Figure 7.

Model for CM-induced preleukemic HSPC alterations and predisposition for leukemia evolution. Somatic expression of CM induces the expansion of preleukemic HSPCs including LSK and Pre-Meg/E progenitors with dysregulated erythroid (Spi-1, Fog1, Gata2, and Gfi1b) and megakaryocytic (Mpl, Pf4, and Vwf4) gene expression program, leading to impaired erythroid and megakaryocytic differentiation. With increased survival and proliferation rates, poorly differentiating preleukemic Pre-Meg/Es accumulate and serve as a cellular reservoir predisposed for additional mutations and AML transformation.