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Phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia
- Source :
- Leukemia
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a 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.
- Subjects :
- Male
0301 basic medicine
Cancer Research
CD52
CD33
Chronic myelomonocytic leukemia
Antigens, CD34
Apoptosis
Mice, SCID
Biology
CD38
Article
Venetoclax
Mice
03 medical and health sciences
0302 clinical medicine
AML
Mice, Inbred NOD
hemic and lymphatic diseases
Tumor Cells, Cultured
medicine
Animals
Humans
Secondary Acute Myeloid Leukemia
Aged
Cell Proliferation
Aged, 80 and over
Leukemia, Myelomonocytic, Chronic
Hematology
Middle Aged
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
Leukemic Stem Cells
Leukemia, Myeloid, Acute
Leukemia
Phenotype
030104 developmental biology
Oncology
Case-Control Studies
030220 oncology & carcinogenesis
NSGS Mice
Neoplastic Stem Cells
Cancer research
Female
sense organs
Interleukin-3 receptor
Stem cell
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....334159bc764015d401df67cce8ed0d46