RUNX1 mutations enhance self-renewal and block granulocytic differentiation in human in vitro models and primary AMLs.

ABSTRACT: To unravel molecular mechanisms by which Runt-related transcription factor 1 (RUNX1) mutations contribute to leukemic transformation, we introduced the RUNX1-S291fs300X mutation in human CD34⁺ stem/progenitor cells and in human induced pluripotent stem cells (iPSCs). In both models, RUNX1mut overexpression strongly impaired myeloid commitment. Instead, self-renewal was enhanced, as shown, by increased long-term culture-initiating cell frequencies and enhanced colony-forming cell replating capacity. Long-term suspension cultures with RUNX1mut-transduced cord blood (CB) CD34⁺ cells continued for more than 100 days, during which the cells displayed an immature granulocyte-macrophage progenitor-like CD34⁺/CD123⁺/CD45RA⁺ phenotype. The CD34

SUBMITTER: Gerritsen M 

PROVIDER: S-EPMC6373749 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature