{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T21:34:33Z","timestamp":1765056873123,"version":"3.46.0"},"reference-count":40,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cytopenias are common in the adult population, with increasing recognition of clonal hematopoiesis and inherited syndromes due to widespread molecular testing. Clonal hematopoiesis is a premalignant spectrum of disorders characterized by a somatic myeloid mutation, including clonal hematopoiesis of indeterminate potential and clonal cytopenia of uncertain significance. Inherited bone marrow failure syndromes (IBMFS) can also be found during workup of incidental cytopenias, even in the absence of other syndromic associations. In clonal cytopenia of uncertain significance, the overall risk of progressing to a myeloid neoplasm can be affected by the type of mutation, number of mutations, and variant allele frequency. Prognostication systems, such as the Clonal Hematopoiesis Risk Score, MN-predict, and Clonal Cytopenia Risk Score, can help determine the risk of malignant progression. Context-dependent factors like chemotherapy, radiation, and smoking can influence this risk. For suspected IBFMS, workup typically includes telomere length testing and chromosomal breakage analysis, along with comprehensive germline testing. If IBMFS is confirmed, further testing may be indicated based on the syndrome, as patients are often at risk of other organ dysfunction and malignancies. In these patients, stem cell transplantation may be indicated.<\/jats:p>","DOI":"10.1182\/hematology.2025000724","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:08:37Z","timestamp":1764943717000},"page":"353-358","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Molecular approach to cytopenia and bone marrow failure"],"prefix":"10.1182","volume":"2025","author":[{"given":"Jayanshu","family":"Jain","sequence":"first","affiliation":[{"name":"The Ohio State University, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma","family":"Borate","sequence":"additional","affiliation":[{"name":"The Ohio State University, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"17","key":"2025120616333277500_hem2025000724C1","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1182\/bloodadvances.2021004355","article-title":"Peripheral blood cytopenias in the aging general population and risk of incident hematological disease and mortality","volume":"5","author":"van Zeventer","year":"2021","journal-title":"Blood Adv"},{"issue":"43","key":"2025120616333277500_hem2025000724C2","doi-asserted-by":"crossref","first-page":"73483","DOI":"10.18632\/oncotarget.19008","article-title":"Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions","volume":"8","author":"Valent","year":"2017","journal-title":"Oncotarget"},{"issue":"26","key":"2025120616333277500_hem2025000724C3","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N Engl J Med"},{"issue":"26","key":"2025120616333277500_hem2025000724C4","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1182\/blood.2023022222","article-title":"Causes and consequences of clonal hematopoiesis","volume":"142","author":"Weeks","year":"2023","journal-title":"Blood"},{"key":"2025120616333277500_hem2025000724C5","doi-asserted-by":"crossref","first-page":"12484","DOI":"10.1038\/ncomms12484","article-title":"Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults","volume":"7","author":"Young","year":"2016","journal-title":"Nat Commun"},{"issue":"1","key":"2025120616333277500_hem2025000724C6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2015-03-631747","article-title":"Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes","volume":"126","author":"Steensma","year":"2015","journal-title":"Blood"},{"issue":"25","key":"2025120616333277500_hem2025000724C7","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1182\/blood-2017-01-763425","article-title":"Clinical significance of somatic mutation in unexplained blood cytopenia","volume":"129","author":"Malcovati","year":"2017","journal-title":"Blood"},{"issue":"8","key":"2025120616333277500_hem2025000724C8","first-page":"1135","article-title":"Molecular pathways in clonal hematopoiesis: from the acquisition of somatic mutations to transformation into hematologic neoplasm","volume":"12","author":"Gaulin","year":"2022","journal-title":"Life (Basel)"},{"issue":"11","key":"2025120616333277500_hem2025000724C9","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1038\/s41591-021-01521-4","article-title":"Distinction of lymphoid and myeloid clonal hematopoiesis","volume":"27","author":"Niroula","year":"2021","journal-title":"Nat Med"},{"issue":"11","key":"2025120616333277500_hem2025000724C10","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1182\/blood.2021011323","article-title":"Relationship between clone metrics and clinical outcome in clonal cytopenia","volume":"138","author":"Galli","year":"2021","journal-title":"Blood"},{"issue":"5","key":"2025120616333277500_hem2025000724C11","doi-asserted-by":"crossref","DOI":"10.1056\/EVIDoa2200310","article-title":"Prediction of risk for myeloid malignancy in clonal hematopoiesis","volume":"2","author":"Weeks","year":"2023","journal-title":"NEJM Evid"},{"issue":"7","key":"2025120616333277500_hem2025000724C12","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic\/ dendritic neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"issue":"11","key":"2025120616333277500_hem2025000724C13","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"issue":"16","key":"2025120616333277500_hem2025000724C14","first-page":"7059","article-title":"Outcome of TP53-mutated CCUS and the risk of progression to myeloid neoplasms","volume":"41","author":"Li","year":"2023","journal-title":"JCO"},{"issue":"7714","key":"2025120616333277500_hem2025000724C15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41586-018-0317-6","article-title":"Prediction of acute myeloid leukaemia risk in healthy individuals","volume":"559","author":"Abelson","year":"2018","journal-title":"Nature"},{"issue":"9","key":"2025120616333277500_hem2025000724C16","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41588-023-01472-1","article-title":"Multiparameter prediction of myeloid neoplasia risk","volume":"55","author":"Gu","year":"2023","journal-title":"Nat Genet"},{"issue":"19","key":"2025120616333277500_hem2025000724C17","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1182\/blood.2024024756","article-title":"Risk prediction for clonal cytopenia: multicenter real-world evidence","volume":"144","author":"Xie","year":"2024","journal-title":"Blood"},{"issue":"7831","key":"2025120616333277500_hem2025000724C18","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41586-020-2819-2","article-title":"Inherited causes of clonal haematopoiesis in 97,691 whole genomes","volume":"586","author":"Bick","year":"2020","journal-title":"Nature"},{"issue":"11","key":"2025120616333277500_hem2025000724C19","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41588-020-00710-0","article-title":"Cancer therapy shapes the fitness landscape of clonal hematopoiesis","volume":"52","author":"Bolton","year":"2020","journal-title":"Nat Genet"},{"issue":"22","key":"2025120616333277500_hem2025000724C20","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1182\/blood.2019003539","article-title":"Clonal hematopoiesis evolves from pretreatment clones and stabilizes after end of chemotherapy in patients with MCL","volume":"135","author":"Eskelund","year":"2020","journal-title":"Blood"},{"issue":"19","key":"2025120616333277500_hem2025000724C21","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1182\/bloodadvances.2024012929","article-title":"Impact of cancer therapy on clonal hematopoiesis mutations and subsequent clinical outcomes","volume":"8","author":"Nead","year":"2024","journal-title":"Blood Adv"},{"issue":"6","key":"2025120616333277500_hem2025000724C22","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1038\/s41375-024-02253-3","article-title":"Dynamics of clonal hematopoiesis under DNA-damaging treatment in patients with ovarian cancer","volume":"38","author":"Arends","year":"2024","journal-title":"Leukemia"},{"issue":"1","key":"2025120616333277500_hem2025000724C23","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1182\/blood-2023-190457","article-title":"Impact of PARP inhibitor and platinum therapy on clonal hematopoiesis","volume":"142","author":"Baeten","year":"2023","journal-title":"Blood"},{"issue":"16","key":"2025120616333277500_hem2025000724C24","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1182\/blood.2021014956","article-title":"Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms","volume":"140","author":"Sperling","year":"2022","journal-title":"Blood"},{"issue":"5","key":"2025120616333277500_hem2025000724C25","doi-asserted-by":"crossref","first-page":"e7093","DOI":"10.1002\/cam4.7093","article-title":"Cancer patients with clonal hematopoiesis die from primary malignancy or comorbidities despite higher rates of transformation to myeloid neoplasms","volume":"13","author":"Chien","year":"2024","journal-title":"Cancer Med"},{"issue":"10","key":"2025120616333277500_hem2025000724C26","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1038\/s41375-020-0896-8","article-title":"Clonal myelopoiesis in the UK Biobank cohort: ASXL1 mutations are strongly associated with smoking","volume":"34","author":"Dawoud","year":"2020","journal-title":"Leukemia"},{"issue":"7","key":"2025120616333277500_hem2025000724C27","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/s41436-020-0783-8","article-title":"Points to consider for reporting of germline variation in patients undergoing tumor testing: a statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"Li","year":"2020","journal-title":"Genet Med"},{"issue":"14","key":"2025120616333277500_hem2025000724C28","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1182\/blood-2016-05-670240","article-title":"How I diagnose and manage individuals at risk for inherited myeloid malignancies","volume":"128","author":"The University of Chicago Hematopoietic Malignancies Cancer Risk Team","year":"2016","journal-title":"Blood"},{"issue":"24","key":"2025120616333277500_hem2025000724C29","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1182\/blood.2022015790","article-title":"Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages","volume":"140","author":"Feurstein","year":"2022","journal-title":"Blood"},{"issue":"14","key":"2025120616333277500_hem2025000724C30","first-page":"1615","article-title":"Clonal hematopoiesis in the inherited bone marrow failure syndromes","volume":"136","author":"Tsai","year":"2020","journal-title":"Blood"},{"issue":"25","key":"2025120616333277500_hem2025000724C31","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1182\/blood.2023019746","article-title":"Natural history study of patients with familial platelet disorder with associated myeloid malignancy","volume":"142","author":"Cunningham","year":"2023","journal-title":"Blood"},{"issue":"4","key":"2025120616333277500_hem2025000724C32","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/bjh.20018","article-title":"Prevalence of cytopenia(s) and somatic variants in patients with DDX41 mutant germline predisposition syndrome","volume":"206","author":"Kusne","year":"2025","journal-title":"Br J Haematol"},{"key":"2025120616333277500_hem2025000724C33","doi-asserted-by":"crossref","first-page":"107344","DOI":"10.1016\/j.leukres.2023.107344","article-title":"Germline predisposition to clonal hematopoiesis","volume":"132","author":"Liu","year":"2023","journal-title":"Leuk Res"},{"issue":"11","key":"2025120616333277500_hem2025000724C34","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1002\/ajh.26321","article-title":"Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes","volume":"96","author":"Martin","year":"2021","journal-title":"Am J Hematol"},{"issue":"1","key":"2025120616333277500_hem2025000724C35","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1182\/blood-2024-203837","article-title":"High-risk CCUS is clinically indistinguishable from low-risk myelodysplastic syndromes\/neoplasms","volume":"144","author":"Xie","year":"2024","journal-title":"Blood"},{"issue":"8","key":"2025120616333277500_hem2025000724C36","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1182\/bloodadvances.2020003976","article-title":"Clinical, molecular, and prognostic comparisons between CCUS and lower-risk MDS: a study of 187 molecularly annotated patients","volume":"5","author":"Li","year":"2021","journal-title":"Blood Adv"},{"key":"2025120616333277500_hem2025000724C37","doi-asserted-by":"crossref","first-page":"1419323","DOI":"10.3389\/frhem.2024.1419323","article-title":"Clonal cytopenia of undetermined significance: definitions, risk and therapeutic targets","volume":"3","author":"Taborda","year":"2024","journal-title":"Front Hematol"},{"issue":"1","key":"2025120616333277500_hem2025000724C38","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1182\/blood-2023-184977","article-title":"Ivosidenib for patients with clonal cytopenia of undetermined significance and mutations in IDH1","volume":"142","author":"Petrone","year":"2023","journal-title":"Blood"},{"issue":"1","key":"2025120616333277500_hem2025000724C39","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1182\/blood-2023-189949","article-title":"A randomized double-blind placebo-controlled phase II multi-center study of inflammation modification of canakinumab to prevent leukemic progression of clonal cytopenias of unknown significance (CCUS): impact study","volume":"142","author":"Borate","year":"2023","journal-title":"Blood"},{"issue":"2","key":"2025120616333277500_hem2025000724C40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease","volume":"377","author":"Jaiswal","year":"2017","journal-title":"N Engl J Med"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2025\/1\/353\/2470118\/353jain.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/hematology\/article-pdf\/2025\/1\/353\/2470118\/353jain.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T21:33:42Z","timestamp":1765056822000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2025\/1\/353\/556899\/Molecular-approach-to-cytopenia-and-bone-marrow"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12,5]]},"published-print":{"date-parts":[[2025,12,5]]}},"URL":"https:\/\/doi.org\/10.1182\/hematology.2025000724","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"type":"print","value":"1520-4391"},{"type":"electronic","value":"1520-4383"}],"subject":[],"published-other":{"date-parts":[[2025,12,5]]},"published":{"date-parts":[[2025,12,5]]}}}