{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:31:22Z","timestamp":1790753482637,"version":"4.1.0"},"reference-count":287,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Hematopoietic stem cells (HSCs) produce all blood cells throughout the life of the organism. However, the high self-renewal and longevity of HSCs predispose them to accumulate mutations. The acquired mutations drive preleukemic clonal hematopoiesis, which is frequent among elderly people. The preleukemic state, although often asymptomatic, increases the risk of blood cancers. Nevertheless, the direct role of preleukemic HSCs is well-evidenced in adult myeloid leukemia (AML), while their contribution to other hematopoietic malignancies remains less understood. Here, we review the evidence supporting the role of preleukemic HSCs in different types of blood cancers, as well as present the alternative models of malignant evolution. Finally, we discuss the clinical importance of preleukemic HSCs in choosing the therapeutic strategies and provide the perspective on further studies on biology of preleukemic HSCs.<\/jats:p>","DOI":"10.3389\/fonc.2024.1308709","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T04:56:58Z","timestamp":1708318618000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["The dark side of stemness \u2013 the role of hematopoietic stem cells in development of blood malignancies"],"prefix":"10.3389","volume":"14","author":[{"given":"Jadwiga","family":"Filipek-Gorza\u0142a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Kwieci\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Szade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Szade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2353\/AJPATH.2006.060312","article-title":"Hematopoietic stem cells: the paradigmatic tissue-specific stem cell","volume":"169","author":"Bryder","year":"2006","journal-title":"Am J Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.86","article-title":"Hematopoietic stem cell: self-renewal versus differentiation","volume":"2","author":"Seita","year":"2010","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1089\/ars.2017.7419","article-title":"Where hematopoietic stem cells live: the bone marrow niche","volume":"29","author":"Szade","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0497-0","article-title":"Population dynamics of normal human blood inferred from somatic mutations","volume":"561","author":"Lee-Six","year":"2018","journal-title":"Nature"},{"key":"B5","article-title":"Hematology: basic principles and practice","author":"Hoffman","year":"2018"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1242\/dev.106575","article-title":"The analysis, roles and regulation of quiescence in hematopoietic stem cells","volume":"141","author":"Nakamura-Ishizu","year":"2014","journal-title":"Dev Camb Engl"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009778","article-title":"Asymmetric organelle inheritance predicts human blood stem cell fate","volume":"139","author":"Loeffler","year":"2022","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000644","article-title":"Symmetric and asymmetric activation of hematopoietic stem cells","volume":"28","author":"Loeffler","year":"2021","journal-title":"Curr Opin Hematol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3304","DOI":"10.1073\/pnas.0511137103","article-title":"Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells","volume":"103","author":"Luckey","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s13238-019-0633-0","article-title":"New paradigms on hematopoietic stem cell differentiation","volume":"11","author":"Cheng","year":"2020","journal-title":"Protein Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(93)90002-A","article-title":"Heterogeneity of hematopoietic stem cells","volume":"5","author":"Uchida","year":"1993","journal-title":"Curr Opin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.05.015","article-title":"Long-term propagation of distinct hematopoietic differentiation programs","volume":"1","author":"Dykstra","year":"2007","journal-title":"In Vivo. 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