不典型急性早幼粒细胞白血病关键发病和全反式维甲酸耐药机制研究进展

Advances in key pathogenesis of atypical acute promyelocytic leukemia and mechanisms of all-trans retinoic acid resistance

由于全反式维甲酸(ATRA)和砷剂的成功应用,PML::RARA融合基因阳性的急性早幼粒细胞白血病(APL)的治疗已经获得极大成功。但仍有部分患者细胞形态、免疫表型和基因表达谱表现为APL表型,但PML::RARA阴性,也被称为不典型APL。在不典型APL患者中已报道20余种维甲酸受体相关的融合基因,并且发现所有可评估的RARG融合基因阳性患者和约半数少见型RARA融合基因阳性患者对ATRA耐药,但目前缺乏相关的分子机制研究。结合第65届美国血液学会年会报告,对我国在不典型APL的关键发病和ATRA耐药机制方面取得的重要进展进行报道。

Due to the successful application of all-trans retinoic acid(ATRA)and arsenic,the treatment of acute promyelocytic leukemia(APL)with PML::RARA fusion gene has achieved great success.However,some patients are presented with APL phenotype in cellular morphology,immunophenotype,and gene expression profile,while PML::RARA is negative,which is known as atypical APL(aAPL).In aAPL patients,more than 20 fusion genes related to retinoic acid receptors have been reported.It has been discovered that all evaluable patients with RARG fusion genes and approximately half of those with rare RARA fusion genes are resistant to ATRA,however,the molecular mechanisms of this resistance remain poorly studied.Combining with the reports in the 65th American Society of Hematology Annual Meeting,this paper reports great progresses of the key pathogenesis of aAPL and ATRA resistance mechanisms.