癌症研究
白血病
干细胞
生物
慢性粒单核细胞白血病
骨髓
髓系白血病
造血
髓样
表型
免疫学
祖细胞
川地34
医学
免疫分型
作者
Gregor Eisenwort,Irina Sadovnik,Alexandra Keller,Daniel Ivanov,Barbara Peter,Daniela Berger,Gabriele Stefanzl,Karin Bauer,Katharina Slavnitsch,Georg Greiner,Karoline V. Gleixner,Wolfgang R. Sperr,Michael Willmann,Heinz Sill,Peter Bettelheim,Klaus Geissler,Michael W. Deininger,Thomas Rülicke,Peter Valent
出处
期刊:Leukemia
[Springer Nature]
日期:2021-03-30
卷期号:35 (11): 1-12
被引量:3
标识
DOI:10.1038/s41375-021-01227-z
摘要
Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes, and substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34+/CD38- fraction of the malignant clone. Whereas CD34+/CD38- cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34+/CD38+ progenitors or the bulk of CD34- monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34+/CD38- cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies.
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