Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia.


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.

Authors: Eisenwort G, Sadovnik I, Keller A, Ivanov D, Peter B, Berger D, Stefanzl G, Bauer K, Slavnitsch K, Greiner G, Gleixner KV, Sperr WR, Willmann M, Sill H, Bettelheim P, Geissler K, Deininger M, Rülicke T, Valent P,
Journal: Leukemia; 2021 Mar 30 . doi:10.1038/s41375-021-01227-z
Year: 2021
PubMed: PMID: 33785864 (Go to PubMed)