The prognostic significance of genetics in acute myeloid leukemia under venetoclax-based treatment.

IF 3 3区医学 Q2 HEMATOLOGY Annals of Hematology Pub Date : 2024-10-29 DOI:10.1007/s00277-024-06050-x

Shan Zheng, Yuxin Tong, Linlin Yang, Jiayi Chen, Yamin Tan

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Abstract

Acute myeloid leukemia (AML) is the most prevalent hematologic malignancy in adults. In 2022, the European LeukemiaNet (ELN) has updated its prognostic system that incorporates cytogenetics and molecular genetics based on data from patients undergoing intensive chemotherapy (IC). Recently, a risk stratification framework has been established for hypomethylating agents (HMA)-based low-intensity treatment (LIT) to fill the gaps in stratification for this treatment modality, but this needs further refinement. Venetoclax (VEN), a BH3 mimetic, targets BCL-2 to modulate apoptosis and metabolism in AML cells. Its combination with HMA or low-dose cytarabine (LDAC) has been shown to enhance the response rates and prolong the survival outcomes of older or unfit patients with AML. In this review, we delved into the prognostic significance of FLT3-ITD and IDH mutations when used in combination with VEN and HMA, as well as in conjunction with their specific inhibitors. We also explored the role of VEN in NPM1-mutated AML and its efficacy in splicing factor mutations AML. Additionally, we examined the response rates and survival outcomes of CBF-AML when treated with a VEN-based regimen. Moving forward, it is imperative that risk stratification for LIT becomes more nuanced to better align with the requirements of personalized diagnosis and treatment strategies.

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以 Venetoclax 为基础的急性髓性白血病治疗中遗传学的预后意义。

急性髓性白血病（AML）是成人中发病率最高的血液系统恶性肿瘤。2022 年，欧洲白血病网络（ELN）根据接受强化化疗（IC）患者的数据更新了预后系统，将细胞遗传学和分子遗传学纳入其中。最近，为基于低甲基化药物（HMA）的低强度治疗（LIT）建立了一个风险分层框架，以填补这种治疗方式在分层方面的空白，但这还需要进一步完善。Venetoclax（VEN）是一种BH3模拟物，以BCL-2为靶点，调节急性髓细胞白血病细胞的凋亡和代谢。它与HMA或低剂量阿糖胞苷（LDAC）联合治疗已被证明可提高老年或体质较差的急性髓细胞性白血病患者的应答率并延长其生存期。在这篇综述中，我们深入研究了 FLT3-ITD 和 IDH 突变与 VEN 和 HMA 联用以及与它们的特定抑制剂联用时的预后意义。我们还探讨了 VEN 在 NPM1 突变急性髓细胞白血病中的作用及其在剪接因子突变急性髓细胞白血病中的疗效。此外，我们还研究了使用基于 VEN 的方案治疗 CBF-AML 时的反应率和生存结果。展望未来，LIT 的风险分层必须变得更加细致，以更好地满足个性化诊断和治疗策略的要求。

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

Annals of Hematology 医学-血液学

CiteScore

5.60

自引率

2.90%

发文量

304

审稿时长

2 months

期刊介绍： Annals of Hematology covers the whole spectrum of clinical and experimental hematology, hemostaseology, blood transfusion, and related aspects of medical oncology, including diagnosis and treatment of leukemias, lymphatic neoplasias and solid tumors, and transplantation of hematopoietic stem cells. Coverage includes general aspects of oncology, molecular biology and immunology as pertinent to problems of human blood disease. The journal is associated with the German Society for Hematology and Medical Oncology, and the Austrian Society for Hematology and Oncology.