RARA and acute promyelocytic leukemia: Previous studies have demonstrated two essential roles for Irf8 in the regulation of normal myeloid differentiation: promoting the maturation of the monocytic lineage at the expense of granulocytic maturation from GMPs and the terminal maturation or survival of two types of dendritic cells (DCs).28, 38, 39, 40 Therefore, we hypothesized that Irf8 repression served as a key PML/RARα-driven oncogenic mechanism to restrict monocytic/dendritic differentiation leakage of the APL progenitors, which otherwise would erode their leukemogenic potential.