Retinoic Acid in Myeloid Differentiation and Acute Promyelocytic Leukemia (APL)

APL is characterized by chromosomal translocations that generate oncogenic RARα fusion proteins and its clinical response to RA. Two major fusion proteins, PML-RARα and PLZF-RARα, inhibit RA signaling and block myeloid differentiation at physiological concentrations of RA, while pharmacological concentrations of RA activate PML-RARα, but not PLZF-RARα, consistent with the fact that PLZF-RARα-positive APL is resistant to RA treatment.