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[异柠檬酸脱氢酶1/2突变型急性髓系白血病的代谢与治疗]

[Metabolism and therapy in acute myeloid leukemia with isocitrate dehydrogenase 1/2 mutations].

作者信息

Gabellier Ludovic, Bosetta Enzo, Heiblig Maël, Sarry Jean-Emmanuel

机构信息

Service d'hématologie clinique, Centre Hospitalier Universitaire de Montpellier, Montpellier, France - Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Université de Montpellier, Montpellier, France.

Centre de recherches en cancérologie de Toulouse, Inserm U1037, Université de Toulouse, Toulouse, France.

出版信息

Med Sci (Paris). 2025 Apr;41(4):355-366. doi: 10.1051/medsci/2025045. Epub 2025 Apr 28.

Abstract

Isocitrate dehydrogenase IDH1 and IDH2, key enzymes in central and energy metabolism, are frequently mutated in acute myeloid leukemia (AML). They catalyze the production of the oncometabolite R-2-hydroxyglurate, which plays a key role in leukemogenesis and relapse of patients after standard AML treatments. Although the recent introduction of selective inhibitors of IDH1 (ivosidenib) and IDH2 (enasidenib) has improved the prognosis of patients with IDH1- and IDH2-mutant AML, several mechanisms of resistance to these treatments have already been identified, including metabolic reprogramming. The study of these mechanisms has opened up new therapeutic opportunities for the monitoring and treatment of patients with this subtype of AML.

摘要

异柠檬酸脱氢酶IDH1和IDH2是中枢和能量代谢中的关键酶,在急性髓系白血病(AML)中经常发生突变。它们催化致癌代谢物R-2-羟基戊二酸的产生,该物质在白血病发生以及AML患者接受标准治疗后的复发中起关键作用。尽管最近引入的IDH1选择性抑制剂(艾伏尼布)和IDH2选择性抑制剂(恩西地平)改善了IDH1和IDH2突变型AML患者的预后,但已经确定了几种对这些治疗的耐药机制,包括代谢重编程。对这些机制的研究为监测和治疗这种AML亚型的患者开辟了新的治疗机会。

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