Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia
- 30 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 35 (11), 3176-3187
- https://doi.org/10.1038/s41375-021-01227-z
Abstract
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.Funding Information
- Austrian Science Fund (F4704-B20, P30625-B28)
- Medizinische Universität Wien
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