PU.1: An ETS family transcription factor that regulates leukemogenesis besides normal hematopoiesis

The hematopoietic transcription factor PU.1, which is required for lymphomyeloid differentiation of stem cells, was originally identified as an oncogene. In erythroid progenitors, the integration of spleen focus-forming virus (SFFV) into the PU.1 locus causes its overexpression, which blocks their terminal differentiation into erythrocytes and ultimately leads to the development of erythroleukemia. However, in myeloid lineages, PU.1 promotes granulocytic and monocytic differentiation, and graded reduction in its expression blocks their differentiation or maturation and thereby causes myelogenous leukemia. Thus, in addition to normal hematopoietic regulation, PU.1 plays a significant role in leukemogenesis. In the following review, we have consolidated our understanding of the role of transcription factor PU.1 in the development of erythroid as well myeloid leukemia.