Contribution of mutant HSC clones to immature and mature cells in MDS and CMML, and variations with AZA therapy.

ABSTRACT: Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic

SUBMITTER: Schnegg-Kaufmann AS 

PROVIDER: S-EPMC10651766 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature