Advances in RARa fusion genes in acute promyelocytic leukemia

Retinoic acid receptor a (RARa) is a ligand-dependent transcription factor that dimerizes with retinoid X receptor a (RXRa) to activate target gene promoters, playing a critical role in normal hematopoiesis and granulocyte differentiation. The translocation of chromosomes 15 and 17 generates the promyelocytic leukemia-retinoic acid receptor a (PML-RARa) fusion gene, the master driver of acute promyelocytic leukemia (APL). The PML-RARa oncoprotein exerts two major effects: transcriptional repression and disruption of promyelocytic leukemia (PML) function. The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has significantly improved the complete remission rate in APL, making it a highly treatable disease. However, resistance to ATRA/ATO and the emergence of variant fusion genes remain significant challenges to improving APL prognosis. This review provides an overview of the physiological role of retinoid nuclear receptor signaling in hematopoiesis, the pathological mechanisms of PML-RARa in APL, the pharmacologic effects of ATRA/ATO, and the variant translocations identified in APL. We aimed to provide innovative research perspectives and insights that may be applicable to other hematopoietic malignancies. (c) 2025 International Society for Experimental Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.