Function of RARalpha during the maturation of neutrophils.
The retinoic acid receptor alpha gene is the target of chromosomal rearrangements in all cases of acute promyelocytic leukemia (APL). This recurrent involvement of RARalpha 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. RARalpha 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.
Kastner
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, 1 rue Laurent Fries, BP163, 67404 Illkirch Cedex, C.U. de Strasbourg, France.
Chan
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin