Regulation of the hematopoietic cell kinase (HCK) by PML/RARα and PU.1 in acute promyelocytic leukemia.

This study investigates the dynamic regulation of human hematopoietic cell kinase (HCK) in acute promyelocytic leukemia (APL) and the underlying molecular mechanisms. First, the level of HCK in APL blasts was found lower than that in normal granulocytes and monocytes. Second, the HCK promoter was repressed by PML/RARα and this repression required PU.1. PU.1 was capable of transactivating the HCK promoter through a region encompassing three PU.1 motifs. Chromatin immunoprecipitation assays provided evidence that PU.1 and PML/RARα bound to the HCK promoter in vivo. Finally, we found an unequivocal increase of HCK expression upon treatment with all-trans retinoic acid.