Dot1L is required for the expansion of erythroid but not myeloid progenitor cells. Common myeloid progenitor (CMP) cells differentiate along the erythroid (Bfu-E) or myeloid (CFU-GM) lineage. During erythroid differentiation GATA-2 is up-regulated and Pu.1 is down-regulated. During myeloid differentiation GATA-2 is down-regulated and Pu.1 levels increase. Dot1L deficiency causes a block in the proliferation and survival of erythroid progenitor cells, which is in part due to decreased expression of GATA-2 and increased expression of Pu.1.