用于急性白血病患者的 Revumenib:分化治疗的新工具。

IF 8.2 1区 医学 Q1 HEMATOLOGY Haematologica Pub Date : 2024-11-01 DOI:10.3324/haematol.2022.282621
Meira Yisraeli Salman, Eytan M Stein
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引用次数: 0

摘要

急性白血病的治疗正逐渐摆脱 "一刀切 "的方法,因为科学和临床的进步扩大了可用的靶向疗法的范围。这些口服、选择性小分子药物能破坏染色质适配体 Menin 与表观遗传调节因子赖氨酸甲基转移酶 2A (KMT2A) 复合物之间的相互作用。目前已发现两种易感白血病亚型:1)急性髓性白血病(AML),核嗜蛋白 1(NPM1)发生突变;2)任何急性白血病,髓性或淋巴性,发生易位导致 KMT2A 重排。这些白血病都有不同的基因表达,并通过 KMT2A 与梅宁的相互作用得以维持。它们加在一起约占急性髓细胞白血病患者的 40%,急性淋巴细胞白血病患者的 10%。本综述将介绍作为menin抑制剂代表的revumenib从实验室到临床的历程。它将重点介绍对menin抑制剂敏感的白血病的病理生理学、如何将这种认识转化为靶向药物开发以及临床试验数据。此外,还将探讨耐药机制的重要发现,以及使用 menin 抑制剂治疗白血病的未来方向。
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Revumenib for patients with acute leukemia: a new tool for differentiation therapy.

Treatment of acute leukemia is gradually moving away from a "one-size-fits-all" approach, as scientific and clinical advances expand the arsenal of available targeted therapies. One of the recent additions is the group of menin inhibitors; oral, selective, small molecules that disrupt the interaction between the chromatin adapter menin, and an epigenetic regulator, the lysine methyltransferase 2A (KMT2A) complex. Two susceptible leukemia subtypes have been identified: (i) acute myeloid leukemia with a mutation in nucleophosmin 1 (NPM1), and (ii) any acute leukemia, myeloid or lymphoid, with a translocation resulting in the rearrangement of KMT2A. These leukemias share a distinct genetic expression, maintained by the KMT2A-menin interaction. Together they account for approximately 40% of patients with acute myeloid leukemia and 10% of patients with acute lymphoblastic leukemia. This spotlight review follows the journey of revumenib, as a representative of menin inhibitors, from bench to bedside. It focuses on the pathophysiology of leukemias sensitive to menin inhibition, delineation of how this understanding led to targeted drug development, and data from clinical trials. The important discovery of resistance mechanisms is also explored, as well as future directions in the use of menin inhibitors for treating leukemia.

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来源期刊
Haematologica
Haematologica 医学-血液学
CiteScore
14.10
自引率
2.00%
发文量
349
审稿时长
3-6 weeks
期刊介绍: Haematologica is a journal that publishes articles within the broad field of hematology. It reports on novel findings in basic, clinical, and translational research. Scope: The scope of the journal includes reporting novel research results that: Have a significant impact on understanding normal hematology or the development of hematological diseases. Are likely to bring important changes to the diagnosis or treatment of hematological diseases.
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