Proposed novel prosurvival role for RUNX1C in megakaryopoiesis. Models of normal erythroid and megakaryocytic specification (WT, top) and the distinct defects resulting from the complete absence of RUNX1 (RUNX1 null, center) or the specific absence of RUNX1C (P1-MRIPV/MRIPV, bottom). In WT PreMegE progenitors, megakaryocytic and erythroid lineage specification and maturation are carefully regulated to prevent, for example, thrombocytopenia or anemia. By contrast, RUNX1 null PreMegE progenitors undergo impaired maturation, resulting in the production of small, low ploidy megakaryocytes and an increased number of red blood cells containing Howell-Jolly bodies (center). P1-MRIPV/MRIPV PreMegE progenitors, however, undergo altered lineage specification but normal maturation thereafter (bottom).