Function of RARα during the maturation of neutrophils

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Abstract
The retinoic acid receptor α gene is the target of chromosomal rearrangements in all cases of acute promyelocytic leukemia (APL). This recurrent involvement of RARα in the pathogenesis of APL is likely to reflect an important role played by this receptor during the differentiation of immature myeloid cells to neutrophils. RARα is a negative regulator of promyelocyte differentiation when not complexed with RA, and stimulates this differentiation when bound to RA. Since RARs are dispensable for the generation of mature neutrophils, their role thus appears to be to modulatory, rather 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 progenitors to the neutrophil lineage. Thus, the APL translocations target an important regulator of myeloid cell differentiation.