The importance of PU.1 concentration in hematopoietic lineage commitment and maturation

PU.1 is an Ets family transcription factor that is required for the development of myeloid and lymphoid cells. Since PU.1 is required for several different lineages it has been unclear what role PU.1 has in deciding whether a hematopoietic progenitor cell differentiates into a macrophage, granulocyte, or B cell. Recent studies have demonstrated that different cellular concentrations of PU.1 may direct distinct cell fates, with the highest concentrations of PU.1 required for macrophage development and lower concentrations for granulocytic and B-cell fate adoption. Since PU.1 transactivation activity is inhibited by the granulocytic factor, C/EBPalpha and the B-cell factor BSAP, high concentrations of PU.1 may be required for macrophage development in order to overcome the negative effects of alternative lineage specific factors. Lastly, PU.1 upregulation is implicated in the maturation of myeloid cells once they have committed to the macrophage and granulocytic lineages. PU.1 activity is inhibited in some cases of acute myelogenous leukemia (AML), therefore, inhibition of PU.1 induced maturation may be a critical step in leukemogenesis.