Advances of RARα fusion genes in acute promyelocytic leukemia.

IF 2.5 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2025-06-07 DOI:10.1016/j.exphem.2025.104822

Ao Zhang, Shaowei Qiu

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引用次数: 0

Abstract

Retinoic acid receptorα (RARα) is a ligand-dependent transcription factor that dimerizes with retinoid X receptor α (RXRα) to activate target gene promoters, playing a critical role in normal hematopoiesis and granulocyte differentiation. The translocation of chromosomes 15 and 17 generates the PML-RARA fusion gene, the master driver of acute promyelocytic leukemia (APL). The PML-RARα oncoprotein exerts two major effects: transcriptional repression and disruption of 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-RARα in APL, the pharmacological effects of ATRA/ATO, and the variant translocations identified in APL. We aim to provide innovative research perspectives and insights that may be applicable to other hematopoietic malignancies.

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急性早幼粒细胞白血病RARα融合基因的研究进展。

视黄酸受体α (RARα)是一种配体依赖性转录因子，与类视黄酸受体α (RXRα)二聚体激活靶基因启动子，在正常造血和粒细胞分化中起关键作用。15号和17号染色体易位产生PML-RARA融合基因，这是急性早幼粒细胞白血病（APL）的主要驱动基因。PML- rar α癌蛋白具有两种主要作用：转录抑制和PML功能破坏。全反式维甲酸（ATRA）和三氧化二砷（ATO）的引入显著提高了APL的完全缓解率，使其成为一种高度可治疗的疾病。然而，对ATRA/ATO的耐药性和变异融合基因的出现仍然是改善APL预后的重大挑战。本文就维甲酸核受体信号在造血中的生理作用、PML-RARα在APL中的病理机制、ATRA/ATO的药理作用以及APL中发现的变异型易位进行综述。我们的目标是提供创新的研究视角和见解，可能适用于其他造血恶性肿瘤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

期刊介绍： Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.