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(PDF) Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis
<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="MvEntt-HL7Gghx5VfiMXnuaOamwOnc5pvHn61PndYXWGGNkuc3UZEVaUq9YoVI83vVrPCy_NE4SiFwzmS1DJfQ" /> <meta name="citation_title" content="Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis" /> <meta name="citation_publication_date" content="1995/01/01" /> <meta name="citation_journal_title" content="American Journal of Hematology" /> <meta name="citation_author" content="Syed Ali" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis" /> <meta name="twitter:title" content="Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis" /> <meta name="twitter:description" content="Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM" /> <meta name="twitter:image" content="https://0.academia-photos.com/5632956/2454002/2852543/s200_syed.ali.jpg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis" /> <meta property="og:title" content="Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM" /> <meta property="article:author" content="https://iqra.academia.edu/Ali" /> <meta name="description" content="Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM" /> <title>(PDF) Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis</title> <link rel="canonical" href="https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '9edfe5ffde42435a7fdbf4ab166bfd436281cd36'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1739917855000); window.Aedu.timeDifference = new Date().getTime() - 1739917855000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end-labeling of DNA directly from BM biopsies, which were simultaneously double-labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S-phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley-Liss, Inc.","author":[{"@context":"https://schema.org","@type":"Person","name":"Syed Ali","url":"https://iqra.academia.edu/Ali"}],"contributor":[],"dateCreated":"2013-09-18","dateModified":"2015-12-16","datePublished":"1995-01-01","headline":"Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis","image":"https://attachments.academia-assets.com/49805119/thumbnails/1.jpg","inLanguage":"en","keywords":[],"publication":"American Journal of Hematology","publisher":{"@context":"https://schema.org","@type":"Organization","name":null},"sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":"iqra"}],"thumbnailUrl":"https://attachments.academia-assets.com/49805119/thumbnails/1.jpg","url":"https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis"}</script><style type="text/css">@media(max-width: 567px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 #22223340;--primary-brand: #0645b1;--error-dark: #b60000;--success-dark: #05b01c;--inactive-fill: #ebebee;--hover: #0c3b8d;--pressed: #082f75;--button-primary-fill-inactive: #ebebee;--button-primary-fill: #0645b1;--button-primary-text: #ffffff;--button-primary-fill-hover: #0c3b8d;--button-primary-fill-press: #082f75;--button-primary-icon: 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"https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F4525941%2FSimultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis%3Fshow_translation%3Dtrue"; window.loswp.previewableAttachments = [{"id":49805119,"identifier":"Attachment_49805119","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":4525941,"created_at":"2013-09-18T22:27:36.619-07:00","from_world_paper_id":119639820,"updated_at":"2021-01-13T05:15:10.779-08:00","_data":{"abstract":"Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end-labeling of DNA directly from BM biopsies, which were simultaneously double-labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S-phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley-Liss, Inc.","publication_date":"1995,,","publication_name":"American Journal of Hematology"},"document_type":"paper","pre_hit_view_count_baseline":0,"quality":"high","language":"en","title":"Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [5632956]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":49805119,"attachmentType":"pdf"}"><img alt="First page of “Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/49805119/mini_magick20190130-25421-1gs5jka.png?1548881543" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="5632956" href="https://iqra.academia.edu/Ali"><img alt="Profile image of Syed Ali" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/5632956/2454002/2852543/s65_syed.ali.jpg" />Syed Ali</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">1995, American Journal of Hematology</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">12 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 4525941; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end-labeling of DNA directly from BM biopsies, which were simultaneously double-labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S-phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley-Liss, Inc.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":49805119,"attachmentType":"pdf","workUrl":"https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":49805119,"attachmentType":"pdf","workUrl":"https://www.academia.edu/4525941/Simultaneous_assessment_of_cell_kinetics_and_programmed_cell_death_in_bone_marrow_biopsies_of_myelodysplastics_reveals_extensive_apoptosis_as_the_probable_basis_for_ineffective_hematopoiesis"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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Detailed cell cycle kinetics were examined following in vivo infusions of iodo--and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apoptosis was measured by in situ end labeling (ISEL) of fragmented DNA. Results showed that MDS are highly proliferative disorders with an equally high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy sections for ISEL/BrdU we found the peculiar situation of &quot;signal antonymy&quot; where S-phase cells were frequently apoptotic, a phenomenon so far only seen in MDS biopsies. The cause-effect relationship of this excessive proliferation/apoptosis is discussed at length.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Excessive proliferation matched by excessive apoptosis in myelodysplastic syndromes: the cause-effect relationship","attachmentId":91380626,"attachmentType":"pdf","work_url":"https://www.academia.edu/87064091/Excessive_proliferation_matched_by_excessive_apoptosis_in_myelodysplastic_syndromes_the_cause_effect_relationship","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/87064091/Excessive_proliferation_matched_by_excessive_apoptosis_in_myelodysplastic_syndromes_the_cause_effect_relationship"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="82639663" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/82639663/Apoptosis_in_bone_marrow_biopsy_samples_involving_stromal_and_hematopoietic_cells_in_50_patients_with_myelodysplastic_syndromes_see_comments_">Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes [see comments]</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="59016863" href="https://independent.academia.edu/AGAPIPARCHARIDOU">AGAPI PARCHARIDOU</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Blood, 1995</p><p class="ds-related-work--abstract ds2-5-body-sm">Cell-cycle kinetics were measured in situ after infusions of iododeoxyuridine and/or bormodeoxyuridine in 50 patients with myelodysplastic syndromes (MDS) and the median labeling index in bone marrow (BM) biopsy samples was 28.6%. Unfortunately, 26 of 50 patients showed that &gt; or = 75% of hematopoietic cells of all three lineages were undergoing programmed cell death (PCD) in their biopsy samples as shown by the in situ end labeling (ISEL) technique. Ten patients had 1/3 and eight had 2/3 ISEL+ cells. Stromal cells were frequently ISEL+ and often S-phase cells were also found to be simultaneously ISEL+. Nucleosomal DNA fragments as a ladder in agarose gel were present in BM aspirates of four patients who showed high ISEL and were absent in two who had no ISEL staining in biopsy samples, but only when DNA was extracted after a 4-hour in vitro incubation in complete medium. Therefore, laddering data confirmed the ISEL findings that the majority of hematopoietic cells in MDS are in ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes [see comments]","attachmentId":88280068,"attachmentType":"pdf","work_url":"https://www.academia.edu/82639663/Apoptosis_in_bone_marrow_biopsy_samples_involving_stromal_and_hematopoietic_cells_in_50_patients_with_myelodysplastic_syndromes_see_comments_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/82639663/Apoptosis_in_bone_marrow_biopsy_samples_involving_stromal_and_hematopoietic_cells_in_50_patients_with_myelodysplastic_syndromes_see_comments_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="26047806" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26047806/The_role_of_apoptosis_in_regulating_hematopoietic_stem_cell_numbers">The role of apoptosis in regulating hematopoietic stem cell numbers</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49623675" href="https://independent.academia.edu/JosDomen">Jos Domen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Apoptosis : an international journal on programmed cell death, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">The importance of apoptosis, in combination with proliferation, in maintaining stable populations has become increasingly clear in the last decade. Perturbation of either of these processes can have serious consequences, and result in a variety of disorders. Moreover, as the players and pathways gradually emerge, it turns out that there are strong connections in the regulation of cell cycle progression and apoptosis. Apoptosis, proliferation, and the disorders resulting from aberrant regulation have been studied in a variety of cell types and systems. Hematopoietic stem cells (HSC) are defined as primitive mesenchymal cells that are capable of both self-renewal and differentiation into the various cell lineages that constitute the functioning hematopoietic system. Many (but certainly not all) mature hematopoietic cells are relatively short-lived, sometimes with a half-life in the order of days. Homeostasis requires the production of 10(8) (mouse) to 10(11) (human) cells each day. Al...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The role of apoptosis in regulating hematopoietic stem cell numbers","attachmentId":46386130,"attachmentType":"pdf","work_url":"https://www.academia.edu/26047806/The_role_of_apoptosis_in_regulating_hematopoietic_stem_cell_numbers","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26047806/The_role_of_apoptosis_in_regulating_hematopoietic_stem_cell_numbers"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="55604154" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55604154/Incidence_and_role_of_apoptosis_in_myelodysplastic_syndrome_morphological_and_ultrastructural_assessment">Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="15465688" href="https://independent.academia.edu/VladimirBumbasirevic">Vladimir Bumbasirevic</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Leukemia, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">By application of morphological and ultrastructural methods nosis. The pathogenesis of MDS is still unclear. It has been for identification of apoptosis, we analyzed the incidence of found that oncogene dysregulation is the basis of the disease. morphologically evident apoptosis in the bone marrow of 30 The paradox of persistent pancytopenia in peripheral blood patients with myelodysplastic syndrome (MDS), and in the with hypercellular bone marrow in most cases of MDS is bone marrow of 12 healthy individuals. According to FAB explained by the term 'ineffective hematopoiesis' but the real classification, out of 30 patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia with ringed sidero-mechanism responsible has not been explained yet. It has blasts, 14 (46.6%) had refractory anemia with excess of blasts been hypothesized that the mechanism of apoptosis may be and two (6.8%) had refractory anemia with excess of blasts in responsible for the ineffective hematopoiesis in MDS. 4 transformation. Three patients (10%) had chronic myelomono-In this study we analyzed bone marrow samples of 30 cytic leukemia. Cells in apoptosis were examined on semithin patients with MDS in order to evaluate the incidence of slides and expressed as the apoptotic index (AI) (percent counpremature apoptosis, as the morphological equivalent of 'inefted on at least 1000 cells). An overall increase in apoptosis in patients with MDS was found (median AI in patients vs controls, fective hematopoiesis'. 3.13% vs 1.05%, P Ͻ 0.01 by Mann-Whitney U test). Also, negative correlation between AI and white blood cell count was found (linear r = −0.53, or Spearman rank R = −0.52, both Patients and methods P Ͻ 0.01). In patients with evident karyotype changes AI was not higher than in patients with normal karyotype. This sug-Our study included 30 patients with primary MDS stratified gests that discrete alterations in apoptosis are present even in karyotypically 'normal' clones. Our results strongly support the according to criteria of FAB classification. 5 Out of 30 patients, hypothesis that apoptosis has a role in ineffective hematopoeight (26.6%) patients had refractory anemia (RA), three (10%) iesis and may be a mechanism responsible for the paradox of had refractory anemia with ringed sideroblasts (RARS), 14 hypercellular bone marrow and peripheral blood pancytopenia (46.6%) had refractory anemia with excess of blasts (RAEB) in MDS.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment","attachmentId":71398899,"attachmentType":"pdf","work_url":"https://www.academia.edu/55604154/Incidence_and_role_of_apoptosis_in_myelodysplastic_syndrome_morphological_and_ultrastructural_assessment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/55604154/Incidence_and_role_of_apoptosis_in_myelodysplastic_syndrome_morphological_and_ultrastructural_assessment"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="55309963" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55309963/Increased_apoptosis_of_bone_marrow_cells_and_preserved_proliferative_capacity_of_selected_progenitors_predict_for_clinical_response_to_anti_inflammatory_therapy_in_myelodysplastic_syndromes">Increased apoptosis of bone marrow cells and preserved proliferative capacity of selected progenitors predict for clinical response to anti-inflammatory therapy in myelodysplastic syndromes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="43300890" href="https://independent.academia.edu/CecileduToit">Cecile du Toit</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Experimental Hematology, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Objectives. To determine the relation of apoptosis and clonal proliferation in the bone marrow (BM) to the effectiveness of a therapeutic protocol described to downmodulate monokine activity in patients with myelodysplastic syndromes (MDS). Materials and Methods. Prior to protocol therapy, BM stroma was cultivated and selected CD34 ϩ cells were studied in stroma and cytokine-dependent clonogenic assays. The TUNEL assay was used to establish the degree of apoptosis occurring in the marrow and CD34 ϩ population. The effectiveness of oral ciproloxacin 500 mg b.i.d., pentoxifylline 800 mg t.i.d., and dexamathasone 4 mg t.i.d. (CPD) antiinflammatory therapy was correlated with the intensity of cell apoptosis and proliferation of BM progenitor cells. Results. Seventeen patients were studied. Twelve patients (10 transfusion dependent) received therapy for a median of 99 days (range 49-284). Toxicity caused four patients to discontinue the drug combination. Six patients fulfilled response criteria. Four patients became transfusion independent, and 50% reduction in the need for blood transfusions was noted in one patient. Blood parameters of one untransfused patient increased by Ͼ 30%. Blood count remained unsupported in three patients, even at a median of 12 months after trial discontinuation. Apoptosis of marrow cells and selected CD34 ϩ progenitors was detected in a median of 49.5% (range 3.6%-90%) and 10.6% (range 3.6%-100%; p Ͻ 0.01), respectively. In patients who responded to therapy, the median apoptosis rate in the bone marrow population was 71%, in contrast to the nonresponder's rate of 13% (p ϭ 0.002). Overall clonogenic growth of selected precursors corresponded significantly with response to CPD protocol (p ϭ 0.004). Conclusions. In some patients with MDS, ineffective hematopoiesis is related to high apoptotic index despite proliferation of the CD34 ϩ precursors. These patients seem to benefit from CPD cytokine modulatory therapeutic strategy.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased apoptosis of bone marrow cells and preserved proliferative capacity of selected progenitors predict for clinical response to anti-inflammatory therapy in myelodysplastic syndromes","attachmentId":71240465,"attachmentType":"pdf","work_url":"https://www.academia.edu/55309963/Increased_apoptosis_of_bone_marrow_cells_and_preserved_proliferative_capacity_of_selected_progenitors_predict_for_clinical_response_to_anti_inflammatory_therapy_in_myelodysplastic_syndromes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/55309963/Increased_apoptosis_of_bone_marrow_cells_and_preserved_proliferative_capacity_of_selected_progenitors_predict_for_clinical_response_to_anti_inflammatory_therapy_in_myelodysplastic_syndromes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="95986158" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/95986158/Altered_oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells">Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42083301" href="https://independent.academia.edu/RRajapaksa">Ranjani Rajapaksa</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Blood, 1996</p><p class="ds-related-work--abstract ds2-5-body-sm">Ineffective hematopoiesis with associated cytopenias and potential evolution to acute myeloid leukemia (AML) characterize patients with myelodysplastic syndrome (MDS). We evaluated levels of apoptosis and of apoptosis-related oncoproteins (c-Myc, which enhances, and Bcl-2, which diminishes apoptosis) expressed within CD34+ and CD34- marrow cell populations of MDS patients (n = 24) to determine their potential roles in the abnormal hematopoiesis of this disorder. Marrow cells were permeabilized and CD34+ and CD34- cells were separately analyzed by FACS to detect: (1) a subdiploid (sub-G1) DNA population, and (2) expression of Bcl-2 and c-Myc oncoproteins. Within the CD34+ subset, a significantly increased percentage of cells demonstrated apoptotic/sub- G1 DNA content in early (ie. refractory anemia) MDS patients compared with normal individuals and AML patients (mean values: 9.1% &gt; 2.1% &gt; 1.2%). Correlated with these findings, the ratio of expression of c-Myc to Bcl-2 oncoprote...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells","attachmentId":98011442,"attachmentType":"pdf","work_url":"https://www.academia.edu/95986158/Altered_oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/95986158/Altered_oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="25912416" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/25912416/Increased_apoptosis_in_bone_marrow_B_lymphocytes_but_not_T_lymphocytes_in_myelodysplastic_syndrome">Increased apoptosis in bone marrow B lymphocytes but not T lymphocytes in myelodysplastic syndrome</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49706980" href="https://mdanderson.academia.edu/MaherAlbitar">Maher Albitar</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="157918264" href="https://independent.academia.edu/HeshamAmin6">Hesham Amin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Blood, 2003</p><p class="ds-related-work--abstract ds2-5-body-sm">The hallmark of myelodysplastic syndrome (MDS) is enhanced apoptosis in myeloid, erythroid, and megakaryocytic cells in the bone marrow leading to ineffective hematopoiesis. Recent studies suggested that immunological and microenvironmental factors play a role in the pathophysiology of this disease. We report a significant increase in apoptosis in bone marrow B lymphocytes in MDS as compared to that found in acute myeloid leukemia and healthy controls. Furthermore, we demonstrate that patients with refractory anemia with excess blasts in transformation (RAEB-T) had apoptosis levels in lymphocytes similar to those seen in other subtypes of MDS. Our findings suggest that the alterations in B lymphocytes in the form of increased apoptosis can be seen in MDS and support the concept that immune modulation plays a role in the pathophysiology of</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased apoptosis in bone marrow B lymphocytes but not T lymphocytes in myelodysplastic syndrome","attachmentId":46274597,"attachmentType":"pdf","work_url":"https://www.academia.edu/25912416/Increased_apoptosis_in_bone_marrow_B_lymphocytes_but_not_T_lymphocytes_in_myelodysplastic_syndrome","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/25912416/Increased_apoptosis_in_bone_marrow_B_lymphocytes_but_not_T_lymphocytes_in_myelodysplastic_syndrome"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="55664655" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55664655/Oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells">Oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42083301" href="https://independent.academia.edu/RRajapaksa">Ranjani Rajapaksa</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Blood</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells","attachmentId":71430011,"attachmentType":"pdf","work_url":"https://www.academia.edu/55664655/Oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/55664655/Oncoprotein_expression_and_apoptosis_in_myelodysplastic_syndrome_marrow_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="110967911" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/110967911/Proliferative_and_anti_apoptotic_fractions_in_maturing_hematopoietic_cell_lineages_and_their_role_in_homeostasis_of_normal_bone_marrow">Proliferative and anti‐apoptotic fractions in maturing hematopoietic cell lineages and their role in homeostasis of normal bone marrow</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="100217342" href="https://independent.academia.edu/HopmanAnton">Anton Hopman</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cytometry Part A</p><p class="ds-related-work--abstract ds2-5-body-sm">Recent developments in clinical flow cytometry allow the simultaneous assessment of proliferative and anti‐apoptotic activity in the different hematopoietic cell lineages and during their maturation process. This can further advance the flow cytometric diagnosis of myeloid malignancies. In this study we established indicative reference values for the Ki‐67 proliferation index and Bcl‐2 anti‐apoptotic index in blast cells, as well as maturing erythroid, myeloid, and monocytic cells from normal bone marrow (BM). Furthermore, the cell fractions co‐expressing both proliferation and anti‐apoptotic markers were quantified. Fifty BM aspirates from femoral heads of patients undergoing hip replacement were included in this study. Ten‐color/twelve‐parameter flow cytometry in combination with a software‐based maturation tool was used for immunophenotypic analysis of Ki‐67 and Bcl‐2 positive fractions during the erythro‐, myelo‐, and monopoiesis. Indicative reference values for the Ki‐67 and Bc...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Proliferative and anti‐apoptotic fractions in maturing hematopoietic cell lineages and their role in homeostasis of normal bone marrow","attachmentId":108620440,"attachmentType":"pdf","work_url":"https://www.academia.edu/110967911/Proliferative_and_anti_apoptotic_fractions_in_maturing_hematopoietic_cell_lineages_and_their_role_in_homeostasis_of_normal_bone_marrow","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/110967911/Proliferative_and_anti_apoptotic_fractions_in_maturing_hematopoietic_cell_lineages_and_their_role_in_homeostasis_of_normal_bone_marrow"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="803090" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/803090/Faris_Q_AL_Enzi_and_Mohamed_L_Salem_The_Hematopoietic_Stem_Cells_Between_Apoptosis_and_Self_renewal_Yale_J_Biology_Medicine_2009_82_7_18">Faris Q. AL-Enzi and Mohamed L. Salem. The Hematopoietic Stem Cells: Between Apoptosis and Self-renewal. Yale J. Biology Medicine 2009, 82:7-18.</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="174532" href="https://tanta.academia.edu/ProfMohamedLabibSalem">Prof. Mohamed Labib Salem</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Self renewal and apoptosis of haemopoietic stem cells (HSC † ) represent major factors that determine the size of the haemopoietic cell mass. Changes in self renewal above or below the steady state value of 0.5 will result in either bone marrow expansion or aplasia, respectively. Despite the growing body of research that describes the potential role of HSC, there is still very little information on the mechanisms that govern HSC self renewal and apoptosis. Considerable insight into the role of HSC in many diseases has been gained in recent years. In light of their crucial importance, this article reviews recent developments in the understanding of the molecular, biological, and physiological characteristics of haemopoietic stem cells.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Faris Q. AL-Enzi and Mohamed L. Salem. The Hematopoietic Stem Cells: Between Apoptosis and Self-renewal. Yale J. Biology Medicine 2009, 82:7-18.","attachmentId":4845704,"attachmentType":"pdf","work_url":"https://www.academia.edu/803090/Faris_Q_AL_Enzi_and_Mohamed_L_Salem_The_Hematopoietic_Stem_Cells_Between_Apoptosis_and_Self_renewal_Yale_J_Biology_Medicine_2009_82_7_18","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/803090/Faris_Q_AL_Enzi_and_Mohamed_L_Salem_The_Hematopoietic_Stem_Cells_Between_Apoptosis_and_Self_renewal_Yale_J_Biology_Medicine_2009_82_7_18"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":49805119,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":49805119,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_49805119" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="26047776" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26047776/The_Role_of_Apoptosis_in_Regulating_Hematopoiesis_and_Hematopoietic_Stem_Cells">The Role of Apoptosis in Regulating Hematopoiesis and Hematopoietic Stem Cells</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49623675" href="https://independent.academia.edu/JosDomen">Jos Domen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Immunologic Research, 2000</p><div 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href="https://www.academia.edu/10313064/Uncontrolled_triggering_of_programmed_cell_death_apoptosis_in_haematopoietic_stem_cells_A_new_hypothesis_for_the_pathogenesis_of_aplastic_anaemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="76908221" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/76908221/Massive_apoptosis_of_bone_marrow_cells_in_aplastic_anaemia">Massive apoptosis of bone marrow cells in aplastic anaemia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="24457909" href="https://independent.academia.edu/NareshTripathy">Naresh Tripathy</a></div><p class="ds-related-work--metadata ds2-5-body-xs">British Journal of Haematology, 2002</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Massive apoptosis of bone marrow cells in aplastic anaemia","attachmentId":84460435,"attachmentType":"pdf","work_url":"https://www.academia.edu/76908221/Massive_apoptosis_of_bone_marrow_cells_in_aplastic_anaemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/76908221/Massive_apoptosis_of_bone_marrow_cells_in_aplastic_anaemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" 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href="https://independent.academia.edu/HeidrunKarlic">Heidrun Karlic</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Critical Reviews in Oncology/Hematology, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The role of epigenetics in the regulation of apoptosis in myelodysplastic syndromes and acute myeloid leukemia","attachmentId":44981153,"attachmentType":"pdf","work_url":"https://www.academia.edu/24653326/The_role_of_epigenetics_in_the_regulation_of_apoptosis_in_myelodysplastic_syndromes_and_acute_myeloid_leukemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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Falcão</a></div><p class="ds-related-work--metadata ds2-5-body-xs">British Journal of Haematology, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased apoptotic cells in bone marrow biopsies from patients with aplastic anaemia","attachmentId":87620584,"attachmentType":"pdf","work_url":"https://www.academia.edu/81648934/Increased_apoptotic_cells_in_bone_marrow_biopsies_from_patients_with_aplastic_anaemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/81648934/Increased_apoptotic_cells_in_bone_marrow_biopsies_from_patients_with_aplastic_anaemia"><span 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="8" data-entity-id="20989256" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20989256/Proliferative_activity_of_bone_marrow_cells_in_primary_dysmyelopoietic_preleukemic_syndromes">Proliferative activity of bone marrow cells in primary dysmyelopoietic (preleukemic) syndromes</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42230658" href="https://unipv.academia.edu/CarlomaurizioMontecucco">Carlomaurizio Montecucco</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer, 1983</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Proliferative activity of bone 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class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/83563990/Cell_cycle_distribution_of_different_cell_compartments_in_normal_versus_reactive_bone_marrow_A_frame_of_reference_for_the_study_of_dysplastic_hematopoiesis">Cell-cycle distribution of different cell compartments in normal versus reactive bone marrow: A frame of reference for the study of dysplastic hematopoiesis</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="8107761" href="https://usal.academia.edu/MariaJara">Maria Jara</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cytometry Part B: Clinical Cytometry, 2011</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cell-cycle distribution of different cell compartments in 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="11" data-entity-id="32287435" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/32287435/Simultaneous_Demonstration_of_Clonal_Chromosome_Abnormalities_and_Apoptosis_in_Individual_Marrow_Cells_in_Myelodysplastic_Syndrome">Simultaneous Demonstration of Clonal Chromosome Abnormalities and Apoptosis in Individual Marrow Cells in Myelodysplastic Syndrome</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="62577974" href="https://independent.academia.edu/XiaoliLi11">Xiao-li Li</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Hematology, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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data-collection-position="13" data-entity-id="6625665" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/6625665/In_vitro_proliferation_and_differentiation_of_erythroid_progenitors_from_patients_with_myelodysplastic_syndromes_evidence_for_Fas_dependent_apoptosis">In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="10727618" href="https://inserm.academia.edu/PatrickMayeux">Patrick Mayeux</a></div><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"In vitro proliferation and differentiation of erythroid progenitors from 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