Function of RAR alpha during the maturation of neutrophils

The retinoic acid receptor alpha gene is the target of chromosomal rearrang ements in all cases of acute promyelocytic leukemia (APL). This recurrent i nvolvement of RAR alpha in the pathogenesis of APL is likely to reflect an important role played by this receptor during the differentiation of immatu re myeloid cells to neutrophils. RAR alpha is a negative regulator of promy elocyte differentiation when not complexed with RA, and stimulates this dif ferentiation when bound to RA. Since RARs are dispensable for the generatio n of mature neutrophils, their role thus appears to be to modulatory, rathe r than obligatory, for the control of neutrophil differentiation. In vitro, retinoic acid is also a potent inducer of neutrophil cell fate, suggesting that it might play a role in the commitment of pluripotent hematopoietic p rogenitors to the neutrophil lineage. Thus, the APL translocations target a n important regulator of myeloid cell differentiation.