A model for lineage skewing and leukemogenesis induced by inv(3)-driven EVI1 expression and GATA2 haploinsufficiency. Inv(3)-driven EVI1 expression promotes expansion of MPP2 and MPP3, and also induces subsequent megakaryopoiesis (all cells encompassed by the red ellipse circle). Gata2 haploinsufficiency has a mild enhancement effect on MPP2 and ST-HSC (green circle). Based on the results that the 3q21q26-EVI1::Gata2^+/gfp-induced leukemias nicely recapitulate major hematological features of patients with 3q AML with elevated Mk and platelet numbers, it is implied that the High Mk/platelet leukemia arises from a cell that could be ST-HSC, MPP2, or a progenitor somewhere between these 2 (purple arrow).