Reprogramming identifies functionally distinct stages of clonal evolution in myelodysplastic syndromes.

ABSTRACT: Myeloid neoplasms, including myelodysplastic syndromes (MDS), are genetically heterogeneous disorders driven by clonal acquisition of somatic mutations in hematopoietic stem and progenitor cells (HPCs). The order of premalignant mutations and their impact on HPC self-renewal and differentiation remain poorly understood. We show that episomal reprogramming of MDS patient samples generates induced pluripotent stem cells from single premalignant cells with a partial complement of mutations, directly informing the temporal order of mutations in the individual patient. Reprogramming preferentially captured early subclones with fewer mutations, which were rare among single patient cells. To evaluate the functional impact of clonal evolution in individual patients, we differentiated isogenic MDS

SUBMITTER: Hsu J 

PROVIDER: S-EPMC6624967 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature