RARG Gene Dysregulation in Acute Myeloid Leukemia

Retinoic acid receptor gamma (RAR gamma) belongs to the nuclear receptor superfamily and shares 90% homology with retinoic acid receptor alpha (RAR alpha) and retinoic acid receptor beta (RAR beta). RARA rearrangements are well-known to be involved in acute promyelocytic leukemia (APL), but RARG rearrangements can also resemble this kind of leukemia. In this review we trace the role of RAR gamma, considering both its physiological and oncogenic contribution; from 2011 to date, nine cases of patients harboring RARG fusions have been reported. These patients showed typical APL features, including the clinical presentation, coagulation abnormalities and morphological features of bone marrow (BM), but are not responsive to APL standard therapy. We stress the urgent need for a better comprehension of the critical role of RARG dysregulation in the leukemogenesis process, since optimum therapy strategies have not yet been established.