Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma

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Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept …"><meta name="keywords" content="pmid:28552327, PMC5571650, doi:10.1016/j.ccell.2017.04.012, Michail S Lionakis, Kieron Dunleavy, Wyndham H Wilson, Adenine / analogs & derivatives, Agammaglobulinaemia Tyrosine Kinase, Aged, Aged, 80 and over, Animals, Aspergillosis / epidemiology, Aspergillosis / immunology, Brain Neoplasms / drug therapy*, Brain Neoplasms / metabolism, CD79 Antigens / genetics, Drug Therapy, Combination, Enzyme Inhibitors / adverse effects, Enzyme Inhibitors / pharmacokinetics, Enzyme Inhibitors / therapeutic use*, Female, Gene Knockout Techniques, Humans, Lymphoma / drug therapy*, Lymphoma / metabolism, Male, Mice, Mice, Knockout, Middle Aged, Myeloid Differentiation Factor 88 / genetics, Piperidines, Protein-Tyrosine Kinases / antagonists & inhibitors, Protein-Tyrosine Kinases / genetics, Protein-Tyrosine Kinases / immunology, Pyrazoles / adverse effects, Pyrazoles / pharmacokinetics, Pyrazoles / therapeutic use*, Pyrimidines / adverse effects, Pyrimidines / pharmacokinetics, Pyrimidines / therapeutic use*, Receptors, Antigen, B-Cell / metabolism, Signal Transduction / drug effects, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/28552327/"><meta property="og:description" content="Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/28552327/"><meta name="twitter:description" content="Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">  <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search">  <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/no-script.css"> </noscript> <meta name="citation_title" content="Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma"> <meta name="citation_authors" content="Lionakis MS;Dunleavy K;Roschewski M;Widemann BC;Butman JA;Schmitz R;Yang Y;Cole DE;Melani C;Higham CS;Desai JV;Ceribelli M;Chen L;Thomas CJ;Little RF;Gea-Banacloche J;Bhaumik S;Stetler-Stevenson M;Pittaluga S;Jaffe ES;Heiss J;Lucas N;Steinberg SM;Staudt LM;Wilson WH;"> <meta name="citation_date" content="06/12/2017"> <meta name="citation_publisher" content="Cancer Cell"> <meta name="citation_journal_title" content="Cancer cell"> <meta name="citation_pmid" content="28552327"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/28552327/"> <meta name="citation_volume" content="31"> <meta name="citation_issue" content="6"> <meta name="citation_doi" content="10.1016/j.ccell.2017.04.012"> <meta name="citation_issn" content="1878-3686"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/28552327/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. 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class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"> <input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"> <div class="choice-group" role="radiogroup"> <ul class="radio-group-items"> <li> <input type="radio" id="collections-action-panel-new" class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="28552327"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S1535-6108(17)30167-8" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=28552327&db=pubmed&nlmid=101130617" title="See full text options at Elsevier Science" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="28552327" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="full text provider logo"><span class="text"> Elsevier Science </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/28552327/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=28552327&db=pubmed&nlmid=101130617" title="Free full text at PubMed Central" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="28552327" ><span class="text"> Free PMC article </span></a> </div> </div> <div class="short-view"> <a href="#" class="full-text-links-button full-text-links-dialog-trigger"> Full text links </a> </div> </div> <div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/28552327/citations/" data-citation-style="nlm" data-pubmed-format-link="/28552327/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="28552327" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger" aria-label="Save article in MyNCBI collections." data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_button" data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F28552327%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="Tg8aF831fzX2LHG2lN9YIVGfCFuL25mwxtopLOijvqDDCiz8zu0mwhroYR1qYbo3"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="sidebar-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="social-sharing"> <h3 class="title"> Share </h3> <ul class="social-sharing-links usa-unstyled-list"> <li> <a 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dropdown-container" hidden aria-label="Dropdown menu for journal Cancer cell"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Cancer+Cell%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Cancer+Cell%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Cancer Cell" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Cancer Cell"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Cell%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Cancer Cell"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Cancer Cell"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Cancer Cell"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2017 Jun 12;31(6):833-843.e5.</span> </div> <span class="citation-doi"> doi: 10.1016/j.ccell.2017.04.012. </span> <span class="secondary-date"> Epub 2017 May 25. </span> </div> <h1 class="heading-title"> Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Lionakis+MS&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michail S Lionakis">Michail S Lionakis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Dunleavy+K&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Kieron Dunleavy">Kieron Dunleavy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Roschewski+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mark Roschewski">Mark Roschewski</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Widemann+BC&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Brigitte C Widemann">Brigitte C Widemann</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Butman+JA&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John A Butman">John A Butman</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Schmitz+R&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Roland Schmitz">Roland Schmitz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Yang+Y&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Yandan Yang">Yandan Yang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Cole+DE&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Diane E Cole">Diane E Cole</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Melani+C&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christopher Melani">Christopher Melani</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Higham+CS&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christine S Higham">Christine S Higham</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Desai+JV&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jigar V Desai">Jigar V Desai</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ceribelli+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michele Ceribelli">Michele Ceribelli</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Chen+L&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lu Chen">Lu Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Thomas+CJ&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Craig J Thomas">Craig J Thomas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Little+RF&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richard F Little">Richard F Little</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gea-Banacloche+J&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Juan Gea-Banacloche">Juan Gea-Banacloche</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Bhaumik+S&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sucharita Bhaumik">Sucharita Bhaumik</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Stetler-Stevenson+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Maryalice Stetler-Stevenson">Maryalice Stetler-Stevenson</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Pittaluga+S&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stefania Pittaluga">Stefania Pittaluga</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Jaffe+ES&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elaine S Jaffe">Elaine S Jaffe</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Heiss+J&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John Heiss">John Heiss</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lucas+N&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nicole Lucas">Nicole Lucas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Steinberg+SM&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Seth M Steinberg">Seth M Steinberg</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Staudt+LM&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Louis M Staudt">Louis M Staudt</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov." href="#full-view-affiliation-8" ref="linksrc=author_aff"> 8 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Wilson+WH&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Wyndham H Wilson">Wyndham H Wilson</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wilsonw@mail.nih.gov." href="#full-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/28552327/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="full-view-affiliation-5" id="full-view-affiliation-5" ><sup class="key">5</sup> Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.</li> <li data-affiliation-id="full-view-affiliation-6" id="full-view-affiliation-6" ><sup class="key">6</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.</li> <li data-affiliation-id="full-view-affiliation-7" id="full-view-affiliation-7" ><sup class="key">7</sup> Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="full-view-affiliation-8" id="full-view-affiliation-8" ><sup class="key">8</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov.</li> <li data-affiliation-id="full-view-affiliation-9" id="full-view-affiliation-9" ><sup class="key">9</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wilsonw@mail.nih.gov.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">28552327</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC5571650&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5571650/" data-ga-category="full_text" data-ga-action="PMCID" > PMC5571650 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1016/j.ccell.2017.04.012&id_type=DOI" href="https://doi.org/10.1016/j.ccell.2017.04.012" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/j.ccell.2017.04.012 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Michail S Lionakis</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Cancer Cell<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2017">2017</time><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/28552327/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="mobile-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> </div> <div class="extended-article-details" id="full-article-details" aria-hidden="true"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="short-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Cancer cell" tabindex="0" aria-controls="short-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Cancer cell" data-pinger-ignore> Cancer Cell </button><div id="short-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Cancer cell"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Cancer+Cell%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Cancer+Cell%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Cancer Cell" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Cancer Cell"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Cell%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Cancer Cell"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Cancer Cell"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Cancer Cell"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2017 Jun 12;31(6):833-843.e5.</span> </div> <span class="citation-doi"> doi: 10.1016/j.ccell.2017.04.012. </span> <span class="secondary-date"> Epub 2017 May 25. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Lionakis+MS&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michail S Lionakis">Michail S Lionakis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Dunleavy+K&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Kieron Dunleavy">Kieron Dunleavy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Roschewski+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mark Roschewski">Mark Roschewski</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Widemann+BC&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Brigitte C Widemann">Brigitte C Widemann</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Butman+JA&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John A Butman">John A Butman</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Schmitz+R&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Roland Schmitz">Roland Schmitz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Yang+Y&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Yandan Yang">Yandan Yang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Cole+DE&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Diane E Cole">Diane E Cole</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Melani+C&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christopher Melani">Christopher Melani</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Higham+CS&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Christine S Higham">Christine S Higham</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Desai+JV&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jigar V Desai">Jigar V Desai</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ceribelli+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Michele Ceribelli">Michele Ceribelli</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Chen+L&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Lu Chen">Lu Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Thomas+CJ&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Craig J Thomas">Craig J Thomas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Little+RF&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richard F Little">Richard F Little</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gea-Banacloche+J&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Juan Gea-Banacloche">Juan Gea-Banacloche</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Bhaumik+S&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sucharita Bhaumik">Sucharita Bhaumik</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Stetler-Stevenson+M&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Maryalice Stetler-Stevenson">Maryalice Stetler-Stevenson</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Pittaluga+S&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stefania Pittaluga">Stefania Pittaluga</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Jaffe+ES&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elaine S Jaffe">Elaine S Jaffe</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Heiss+J&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="John Heiss">John Heiss</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lucas+N&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nicole Lucas">Nicole Lucas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Steinberg+SM&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Seth M Steinberg">Seth M Steinberg</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Staudt+LM&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Louis M Staudt">Louis M Staudt</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov." href="#short-view-affiliation-8" ref="linksrc=author_aff"> 8 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Wilson+WH&cauthor_id=28552327" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Wyndham H Wilson">Wyndham H Wilson</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wilsonw@mail.nih.gov." href="#short-view-affiliation-9" ref="linksrc=author_aff"> 9 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.</li> <li data-affiliation-id="short-view-affiliation-8" id="short-view-affiliation-8" ><sup class="key">8</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov.</li> <li data-affiliation-id="short-view-affiliation-9" id="short-view-affiliation-9" ><sup class="key">9</sup> Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wilsonw@mail.nih.gov.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">28552327</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC5571650&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5571650/" data-ga-category="full_text" data-ga-action="PMCID" > PMC5571650 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1016/j.ccell.2017.04.012&id_type=DOI" href="https://doi.org/10.1016/j.ccell.2017.04.012" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/j.ccell.2017.04.012 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/28552327/citations/" data-citation-style="nlm" data-pubmed-format-link="/28552327/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved complete remission with DA-TEDDi-R. Increased aspergillosis was observed with ibrutinib monotherapy and DA-TEDDi-R. Aspergillosis was linked to BTK-dependent fungal immunity in a murine model. PCNSL is highly dependent on BCR signaling, and ibrutinib appears to enhance the efficacy of chemotherapy. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> ABC DLBCL; Aspergillus fumigatus; B cell receptor signaling; BTK; ibrutinib; macrophage; primary CNS lymphoma. </p> </div> <p class="copyright" id="copyright"> Published by Elsevier Inc. </p> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/7ce884101c14/nihms877934f1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="800" data-image-height="684" data-image-alt="Figure 1" data-pmc-id="PMC5571650" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/e987dc3c68fe/nihms877934f1.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="684"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1. Ibrutinib-chemotherapy cytotoxicity models and DA-TEDDi-R… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1. Ibrutinib-chemotherapy cytotoxicity models and DA-TEDDi-R Schema </p> </strong> <div class="figure-caption-contents"><b> (A) </b> 10 x10 dose titration experiments were…</div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1. Ibrutinib-chemotherapy cytotoxicity models and DA-TEDDi-R Schema </strong> <div class="figure-caption-contents"><b>(A)</b> 10 x10 dose titration experiments were performed by combining a range of ibrutinib concentrations with a range of concentrations of the indicated agents in the TMD8 and OCI-Ly10 ABC DLBCL lines. The DBSumPos metric was used to summarize antagonism across the entire 10 × 10 block whereas the DBSumNeg metric was used to summarize drug synergy. For each selected ibrutinib combination pair, the average, plus or minus the SEM, is shown (2 biological replicates). Representative 10 × 10 dose-titration blocks are shown at the right with dose concentration combinations showing antagonism (blue) or synergy (red) highlighted. (<b>B</b>) DA-TEDDi-R treatment schema. Patients received ibrutinib alone in a 14-day ‘window’ (day -14 to -1) prior to cycle 1 of DA-TEDDi-R (temozolomide, etoposide, liposomal doxorubicin, dexamethasone, ibrutinib and rituximab) with intraventricular cytarabine. Abbreviations: IV- intravenous; PO-by mouth; IT-intrathecal; ICV-intracerebro-ventricular; ANC-absolute neutrophil count.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/6a1f6d66c4b7/nihms877934f2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="800" data-image-height="390" data-image-alt="Figure 2" data-pmc-id="PMC5571650" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/cbe9d6dca9b2/nihms877934f2.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="390"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2. Pharmacokinetics of ibrutinib and metabolite… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2. Pharmacokinetics of ibrutinib and metabolite (PCI-45227) and liposomal doxorubicin </p> </strong> <div class="figure-caption-contents"><b> A. </b> Pharmacokinetics of ibrutinib…</div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2. Pharmacokinetics of ibrutinib and metabolite (PCI-45227) and liposomal doxorubicin </strong> <div class="figure-caption-contents"><b>A.</b> Pharmacokinetics of ibrutinib and it metabolite PCI-45227 at the ibrutinib 840 mg dose level. Data represents the mean and standard deviation of patients 11–18 (8 patients). Ventricular CSF via ommaya reservoir and plasma were drawn during the ibrutinib window prior to day -14; post-dose on day -14 at 1, 2, 4, 6, 8, between 10 to 18, and at 24 hours and assayed for ibrutinib and PCI-45227 as indicated. <b>B.</b> Pharmacokinetics of liposomal doxorubicin in 4 patients. Data represent mean and standard deviation of total doxorubicin concentration (liposome bound + protein bound + free) in plasma and CSF. The mean Cmax in plasma and CSF were 41.4 (range: 23-2–61.5) and 0.61 (range: 0.15–2.83) ng/mL, respectively.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/e102dcafc10e/nihms877934f3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="800" data-image-height="686" data-image-alt="Figure 3" data-pmc-id="PMC5571650" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/ab27877d4f11/nihms877934f3.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="686"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3. Clinical outcome of ibrutinib and… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3. Clinical outcome of ibrutinib and DA-TEDDi-R treatment </p> </strong> <div class="figure-caption-contents"><b> A. </b> Waterfall plot of maximum change…</div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3. Clinical outcome of ibrutinib and DA-TEDDi-R treatment </strong> <div class="figure-caption-contents"><b>A.</b> Waterfall plot of maximum change from baseline of the product of the lesions for subjects with evaluable tumors on ibrutinib alone administered during the ‘window’ from day -14 to day -1 before initiation of DA-TEDDi-R (n=18). Two patients (*) with CSF and intraocular disease were assessed using quantitative estimates of tumor reductions. <b>B.</b> Representative brain MRI image before and after ibrutinib monotherapy in PCNSL patient 1. <b>C.</b> Best overall response rate achieved during DA-TEDDi-R therapy (n=16) and proportion of CR/CRu responses based on the International PCNSL workshop response criteria. The proportion of patients with negative research FDG-PET is shown. <b>D.</b> Swim lane plot of treatment duration and response for all patients on study (n=18). Prior treatment history is indicated by untreated, relapsed or refractory. Relapsed patients recurred following a complete response to prior treatment and refractory patients did not respond to prior chemotherapy. Abbreviations: CR-complete response; CRu-complete response unconfirmed; PR-partial response; PD-progressive disease; SD-stable disease; NE-not evaluable; FDG-PET-fluorodeoxy-glucose-positron emission tomography.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/19dad0e99615/nihms877934f4.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="754" data-image-height="239" data-image-alt="Figure 4" data-pmc-id="PMC5571650" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/9bedea6b1409/nihms877934f4.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="754"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="239"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4. <i> CD79B </i> and <i> MYD88 </i> mutations </p> </strong> <div class="figure-caption-contents"><b> A.… </b></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4. <i> CD79B </i> and <i> MYD88 </i> mutations </p> </strong> <div class="figure-caption-contents"><b> A. </b> Meta-analysis of the prevelance of <i> CD79B </i> ITAM and…</div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4. <i>CD79B</i> and <i>MYD88</i> mutations </strong> <div class="figure-caption-contents"><b>A.</b> Meta-analysis of the prevelance of <i>CD79B</i> ITAM and <i>MYD88</i> L265P mutations in 6 published PCNSL studies, compared with systemic ABC DLBCL. <b>B.</b> <i>CD79B</i> and <i>MYD88</i> sequence analysis of 4 patients on study based on accessions NP_000617 and NP_002459, respectively. The <i>CD79B</i> splice acceptor mutation in patient 5 involves exon 5, which encodes the Y196 residue of the ITAM motif and thus would be predicted to disrupt ITAM function.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/fb1fb5b98098/nihms877934f5.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="638" data-image-height="1019" data-image-alt="Figure 5" data-pmc-id="PMC5571650" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80cf/5571650/ac32088f6ba5/nihms877934f5.gif" alt="Figure 5" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="638"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1019"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5. Association of <i> Aspergillus </i> with ibrutinib </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5. Association of <i> Aspergillus </i> with ibrutinib </p> </strong> <div class="figure-caption-contents"><b> A. </b> <i> Aspergillus </i> event time and dexamethasone exposure. Seven…</div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5. Association of <i>Aspergillus</i> with ibrutinib </strong> <div class="figure-caption-contents"><b>A.</b> <i>Aspergillus</i> event time and dexamethasone exposure. Seven patients developed aspergillosis of which 2 occurred on ibrutinib alone and 5 occurred during DA-TEDDi-R treatment. Five patients were receiving pre-treatment dexamethasone for control of brain edema. The patient numbers correspond to the swim lane numbers in Figure 3D. <b>B.</b> Brain MRI scans of <i>Aspergillus</i> infection in patient 9. MRI T1 post-contrast brain image pre-ibrutinib shows enhancing tumor and 13-days post-ibrutinib institution shows new <i>Aspergillus</i> abscesses and marked reduction in tumor enhancement. FDG-PET scans pre-ibrutinib shows metabolically active tumor and 13-days post-ibrutinib institution shows new metabolically inactive <i>Aspergillus</i> abscesses and marked reduction in metabolically active tumor. <b>C.</b> Chest CT and brain MRI scans of <i>Aspergillus</i> infection in patient 13. Thirteen days post-ibrutinib, chest CT shows new cavitary <i>Aspergillus</i> abscess that was not present pre-ibrutinb. MRI T1 post-contrast brain images show new ring enhancing <i>A</i>spergillus abscesses that were not present pre-ibrutinib. <b>D.</b> Survival in murine model of <i>Aspergillus</i> infection in <i>Btk</i><sup>−/−</sup> and <i>Btk</i><sup>+/+</sup> mice. At 14-days of observation after pharyngeal aspiration of <i>Aspergillus fumigatus,</i> 7/26 <i>Btk</i><sup>−/−</sup> mice exhibited mortality compared to 0/20 <i>Btk</i><sup>+/+</sup> mice (p = 0.013; log-rank test) in 3 independent experiments. <b>E.</b> Weight loss in murine model of <i>Aspergillus fumigatus</i> at day 3 post-infection shown with standard error of the mean bars (n = 9–11) (p< 0.0001; unpaired <i>t</i>-test). <b>F.</b> Histology of representative lung sections from murine model of A<i>spergillus fumigatus</i> infection at day 4 post-infection (n = 7 <i>Btk</i><sup>−/−</sup> and wild-type mice). Hematoxylin and eosin stain mages in upper panels (scale bars, 500 μm). Note more extensive peribronchial mononuclear cell and neutrophil inflammation with focal interstitial pneumonia and large airway mucous plugs in <i>Btk</i><sup>−/−</sup> compared to <i>Btk</i><sup>+/+</sup> mice lung as pointed out by arrows. Grocott-Gomori’s methenamine silver stain (GMS) images in lower panels demonstrate more extensive <i>Aspergillus fumigatus</i> conidia in <i>Btk</i><sup>−/−</sup> compared to <i>Btk</i><sup>+/+</sup> mice as pointed out by arrows. <b>G.</b> Model of BTK and macrophage innate immunity to <i>Aspergillus</i>. Pulmonary macrophages are the first line of defense against inhaled <i>Aspergillus</i>. Toll-like receptors (TLRs) initiate signaling and the production of inflammatory cytokines on exposure to fungal conidia spores and hyphae. TLR2 and TLR4 are membrane bound and initiate signaling through BTK, which promotes the nuclear translocation of NF-κB (Horwood et al., 2006). Phagocytosis of <i>Aspergillus fumigatus</i> conidia induces TLR9 recruitment to the phagosome and through BTK, leads to activation of phospholipase Cγ and calcineurin-mediated NFAT nuclear translocation (Herbst et al., 2015). NF-κB acts in synergy with NFAT to produce TNFα that results in neutrophil recruitment. Neutrophils are chemotactically attracted to affected areas by TNFα and chemokines, and destroy fungal hyphae through oxidative and non-oxidative killing (Lionakis and Kontoyiannis, 2003). BTK can also affect the myeloid compartment, where it has a role in the differentiation and function of neutrophils (Fiedler et al., 2011; Stadler et al., 2017). Additionally, glucocorticoids impair the phagocytic, oxidative and chemotactic function of both macrophages and neutrophils, and are a risk factor for invasive aspergillosis infection (Lionakis and Kontoyiannis, 2003).</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="linked-articles" id="linked-commentary"> <h2 class="title"> Comment in </h2> <ul class="item-list usa-unstyled-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/28552326/" ref="article_id=28552326&linksrc=comments_link" data-ga-category="comment_correction" data-ga-action="abstract_page_link" data-ga-label="linked-commentary"> Ibrutinib in PCNSL: The Curious Cases of Clinical Responses and Aspergillosis. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Grommes C, Younes A.</span> <span class="docsum-authors short-authors">Grommes C, et al.</span> <span class="docsum-journal-citation full-journal-citation">Cancer Cell. 2017 Jun 12;31(6):731-733. doi: 10.1016/j.ccell.2017.05.004. 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href="/?term=%22Aged%2C+80+and+over%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Aged%2C+80+and+over%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Aged, 80 and over"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Aged, 80 and over"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Aged%2C+80+and+over" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Aged, 80 and over"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Aged, 80 and over"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Aged, 80 and over"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button 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dropdown-block-link" href="/?term=%22Aspergillosis%2Fepidemiology%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Aspergillosis%2Fepidemiology%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Aspergillosis/epidemiology"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Aspergillosis / epidemiology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Aspergillosis" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Aspergillosis / epidemiology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Aspergillosis/epidemiology"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Aspergillosis/epidemiology"[MeSH]" href="#"> Add to Search 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href="/?term=%22Brain+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Brain+Neoplasms%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Brain Neoplasms/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Brain Neoplasms / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Brain+Neoplasms" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Brain Neoplasms / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Brain Neoplasms/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Brain Neoplasms/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword CD79 Antigens / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-9" aria-expanded="false" data-pinger-ignore> CD79 Antigens / genetics </button><div id="keyword-actions-mesh-terms-9" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword CD79 Antigens / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22CD79+Antigens%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22CD79+Antigens%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="CD79 Antigens/genetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="CD79 Antigens / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=CD79+Antigens" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="CD79 Antigens / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""CD79 Antigens/genetics"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""CD79 Antigens/genetics"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Drug Therapy, Combination" tabindex="0" aria-controls="keyword-actions-mesh-terms-10" aria-expanded="false" data-pinger-ignore> Drug Therapy, Combination </button><div id="keyword-actions-mesh-terms-10" class="keyword-actions-dropdown dropdown 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dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Enzyme Inhibitors / pharmacokinetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-12" aria-expanded="false" data-pinger-ignore> Enzyme Inhibitors / pharmacokinetics </button><div id="keyword-actions-mesh-terms-12" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Enzyme Inhibitors / pharmacokinetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Enzyme+Inhibitors%2Fpharmacokinetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Enzyme+Inhibitors%2Fpharmacokinetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Enzyme Inhibitors/pharmacokinetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Enzyme 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Enzyme Inhibitors / therapeutic use* </button><div id="keyword-actions-mesh-terms-major-13" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Enzyme Inhibitors / therapeutic use*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Enzyme+Inhibitors%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Enzyme+Inhibitors%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Enzyme Inhibitors/therapeutic use"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Enzyme Inhibitors / therapeutic use*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Enzyme+Inhibitors" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Enzyme Inhibitors / therapeutic use*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Enzyme Inhibitors/therapeutic use"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Enzyme Inhibitors/therapeutic use"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Female" tabindex="0" aria-controls="keyword-actions-mesh-terms-14" aria-expanded="false" data-pinger-ignore> Female </button><div id="keyword-actions-mesh-terms-14" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Female"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Female"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Female"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Female" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Female"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Female"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Female"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Gene Knockout Techniques" tabindex="0" aria-controls="keyword-actions-mesh-terms-15" aria-expanded="false" data-pinger-ignore> Gene Knockout Techniques </button><div id="keyword-actions-mesh-terms-15" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Gene Knockout Techniques"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Gene+Knockout+Techniques%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Gene+Knockout+Techniques%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Gene Knockout Techniques"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Gene Knockout Techniques"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" 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class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Lymphoma / drug therapy*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-17" aria-expanded="false" data-pinger-ignore> Lymphoma / drug therapy* </button><div id="keyword-actions-mesh-terms-major-17" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Lymphoma / drug therapy*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Lymphoma%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Lymphoma%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Lymphoma/drug therapy"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Lymphoma / drug therapy*"> Search in PubMed </a></li><li><a class="search-in-mesh-link 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use*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Pyrazoles" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Pyrazoles / therapeutic use*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Pyrazoles/therapeutic use"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Pyrazoles/therapeutic use"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Pyrimidines / adverse effects" tabindex="0" aria-controls="keyword-actions-mesh-terms-31" aria-expanded="false" data-pinger-ignore> Pyrimidines / adverse effects </button><div id="keyword-actions-mesh-terms-31" 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dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Pyrimidines/adverse effects"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Pyrimidines/adverse effects"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Pyrimidines / pharmacokinetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-32" aria-expanded="false" data-pinger-ignore> Pyrimidines / pharmacokinetics </button><div id="keyword-actions-mesh-terms-32" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Pyrimidines / pharmacokinetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" 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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Pyrimidines / therapeutic use*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-33" aria-expanded="false" data-pinger-ignore> Pyrimidines / therapeutic use* </button><div id="keyword-actions-mesh-terms-major-33" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Pyrimidines / therapeutic use*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Pyrimidines%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Pyrimidines%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Pyrimidines/therapeutic use"[MAJR]" data-ga-category="search" 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data-pinger-ignore> Receptors, Antigen, B-Cell / metabolism </button><div id="keyword-actions-mesh-terms-34" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, Antigen, B-Cell / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+Antigen%2C+B-Cell%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Receptors%2C+Antigen%2C+B-Cell%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Receptors, Antigen, B-Cell/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Receptors, Antigen, B-Cell / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Receptors%2C+Antigen%2C+B-Cell" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Receptors, Antigen, B-Cell / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Receptors, Antigen, B-Cell/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Receptors, Antigen, B-Cell/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Signal Transduction / drug effects" tabindex="0" aria-controls="keyword-actions-mesh-terms-35" aria-expanded="false" data-pinger-ignore> Signal Transduction / drug effects </button><div id="keyword-actions-mesh-terms-35" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Signal Transduction / drug effects"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Signal+Transduction%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Signal+Transduction%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Signal Transduction/drug effects"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Signal Transduction / drug effects"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Signal+Transduction" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Signal Transduction / drug effects"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Signal Transduction/drug effects"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Signal Transduction/drug effects"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword CD79 Antigens" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> CD79 Antigens </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword CD79 Antigens"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22CD79+Antigens%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22CD79+Antigens%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="CD79 Antigens"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="CD79 Antigens"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22CD79+Antigens%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="CD79 Antigens"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""CD79 Antigens"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""CD79 Antigens"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Enzyme Inhibitors" tabindex="0" aria-controls="keyword-actions-substances-1" aria-expanded="false" data-pinger-ignore> Enzyme Inhibitors </button><div id="keyword-actions-substances-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Enzyme Inhibitors"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Enzyme+Inhibitors%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Enzyme+Inhibitors%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Enzyme Inhibitors"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Enzyme Inhibitors"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Enzyme+Inhibitors%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Enzyme Inhibitors"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Enzyme Inhibitors"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Enzyme Inhibitors"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword MYD88 protein, human" tabindex="0" aria-controls="keyword-actions-substances-2" aria-expanded="false" data-pinger-ignore> MYD88 protein, human </button><div id="keyword-actions-substances-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword MYD88 protein, human"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22MYD88+protein%2C+human%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22MYD88+protein%2C+human%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="MYD88 protein, human"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="MYD88 protein, human"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22MYD88+protein%2C+human%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="MYD88 protein, human"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""MYD88 protein, human"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""MYD88 protein, human"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Myeloid Differentiation Factor 88" tabindex="0" aria-controls="keyword-actions-substances-3" aria-expanded="false" data-pinger-ignore> Myeloid Differentiation Factor 88 </button><div id="keyword-actions-substances-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Myeloid Differentiation Factor 88"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Myeloid+Differentiation+Factor+88%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Myeloid+Differentiation+Factor+88%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Myeloid 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aria-controls="keyword-actions-substances-4" aria-expanded="false" data-pinger-ignore> Piperidines </button><div id="keyword-actions-substances-4" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Piperidines"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Piperidines%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Piperidines%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Piperidines"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Piperidines"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Piperidines%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Piperidines"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Piperidines"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Piperidines"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Pyrazoles" tabindex="0" aria-controls="keyword-actions-substances-5" aria-expanded="false" data-pinger-ignore> Pyrazoles </button><div id="keyword-actions-substances-5" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Pyrazoles"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Pyrazoles%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Pyrazoles%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Pyrazoles"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Pyrazoles"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Pyrazoles%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Pyrazoles"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Pyrazoles"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Pyrazoles"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Pyrimidines" tabindex="0" aria-controls="keyword-actions-substances-6" aria-expanded="false" data-pinger-ignore> Pyrimidines </button><div id="keyword-actions-substances-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Pyrimidines"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Pyrimidines%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Pyrimidines%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Pyrimidines"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Pyrimidines"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Pyrimidines%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Pyrimidines"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Pyrimidines"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Pyrimidines"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Receptors, Antigen, B-Cell" tabindex="0" aria-controls="keyword-actions-substances-7" aria-expanded="false" data-pinger-ignore> Receptors, Antigen, B-Cell </button><div id="keyword-actions-substances-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Receptors, Antigen, B-Cell"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Receptors%2C+Antigen%2C+B-Cell%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Receptors%2C+Antigen%2C+B-Cell%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Receptors, Antigen, B-Cell"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Receptors, Antigen, B-Cell"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Receptors%2C+Antigen%2C+B-Cell%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Receptors, Antigen, B-Cell"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Receptors, Antigen, B-Cell"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Receptors, Antigen, B-Cell"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword ibrutinib" tabindex="0" aria-controls="keyword-actions-substances-8" aria-expanded="false" data-pinger-ignore> ibrutinib </button><div id="keyword-actions-substances-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword ibrutinib"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22ibrutinib%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22ibrutinib%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="ibrutinib"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="ibrutinib"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22ibrutinib%22" 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Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma - PubMed