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白血病基因突变与耐药性的研究进展

Research progress on gene mutations and drug resistance in leukemia.

作者信息

Ma Xiangyu, Xu Jiamin, Wang Yanan, Fleishman Joshua S, Bing Hao, Yu Boran, Li Yanming, Bo Letao, Zhang Shaolong, Chen Zhe-Sheng, Zhao Libo

机构信息

Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China.

Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China.

出版信息

Drug Resist Updat. 2025 Mar;79:101195. doi: 10.1016/j.drup.2024.101195. Epub 2024 Dec 26.

Abstract

Leukemia is a type of blood cancer characterized by the uncontrolled growth of abnormal cells in the bone marrow, which replace normal blood cells and disrupt normal blood cell function. Timely and personalized interventions are crucial for disease management and improving survival rates. However, many patients experience relapse following conventional chemotherapy, and increasing treatment intensity often fails to improve outcomes due to mutated gene-induced drug resistance in leukemia cells. This article analyzes the association of gene mutations and drug resistance in leukemia. It explores genetic abnormalities in leukemia, highlighting recently identified mutations affecting signaling pathways, cell apoptosis, epigenetic regulation, histone modification, and splicing mechanisms. Additionally, the article discusses therapeutic strategies such as molecular targeting of gene mutations, alternative pathway targeting, and immunotherapy in leukemia. These approaches aim to combat specific drug-resistant mutations, providing potential avenues to mitigate leukemia relapse. Future research with these strategies holds promise for advancing leukemia treatment and addressing the challenges of drug-resistant mutations to improve patient outcomes.

摘要

白血病是一种血癌,其特征是骨髓中异常细胞不受控制地生长,这些异常细胞取代正常血细胞并破坏正常血细胞功能。及时且个性化的干预对于疾病管理和提高生存率至关重要。然而,许多患者在接受传统化疗后会复发,并且由于白血病细胞中基因突变导致的耐药性,增加治疗强度往往无法改善治疗结果。本文分析了白血病中基因突变与耐药性的关联。它探讨了白血病中的基因异常,重点介绍了最近发现的影响信号通路、细胞凋亡、表观遗传调控、组蛋白修饰和剪接机制的突变。此外,本文还讨论了白血病的治疗策略,如基因突变的分子靶向治疗、替代途径靶向治疗和免疫治疗。这些方法旨在对抗特定的耐药突变,为减轻白血病复发提供了潜在途径。采用这些策略的未来研究有望推动白血病治疗的进展,并应对耐药突变的挑战以改善患者的治疗结果。

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