Beyond BCL-2: What drives venetoclax resistance in acute myeloid leukemia?

IF 56.1 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2026-08-10 DOI:10.1016/j.ccell.2026.07.004

Anna Skwarska, Marina Konopleva

引用次数: 0

Abstract

The BCL-2 inhibitor venetoclax has transformed outcomes for older or frail patients with acute myeloid leukemia (AML), and its resistance mechanisms are becoming better defined, including compensatory and lineage-associated switches toward MCL-1 or BCL-xL dependence, oncogenic signaling activation, blast phenotype, and differentiation stage. Additional putative mechanisms-such as emerging BAX mutations, mitochondrial structure remodeling, integrated stress response, and metabolic adaptations, including enhanced amino acid uptake and fatty acid oxidation to sustain oxidative phosphorylation-require further validation.

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超越BCL-2：急性髓性白血病中venetoclax耐药的原因？

BCL-2抑制剂venetoclax已经改变了老年或体弱急性髓性白血病（AML）患者的预后，其耐药机制正在得到更好的定义，包括代偿性和谱系相关的MCL-1或BCL-xL依赖性转换、致癌信号激活、母细胞表型和分化阶段。其他推测的机制，如新出现的BAX突变、线粒体结构重塑、综合应激反应和代谢适应，包括增强氨基酸摄取和脂肪酸氧化以维持氧化磷酸化，需要进一步验证。

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

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.