赖氨酸甲基转移酶2A（KMT2A）异常的急性髓系白血病：近期治疗进展
Acute Myeloid Leukemias with Alterations of Lysine Methyltransferase 2A (KMT2A): Recent Therapeutic Developments.
摘要(中文译文)
涉及赖氨酸甲基转移酶2A（KMT2A）的染色体重排定义了成人急性髓系白血病（AML）中一个遗传学上独特的亚群，占成人病例的10%；在儿童AML中发生率更高。涉及11q23染色体上该基因座的易位导致形成嵌合癌基因伙伴，其中KMT2A的N端部分与多种易位伙伴融合。KMT2A融合伙伴的白血病生成活性与其过度激活KMT2A和HOX靶基因表达的能力有关，这些基因刺激造血干细胞的增殖。KMT2A融合蛋白的致癌活性需要与Menin结合，而这种相互作用可以通过作为强效和选择性Menin抑制剂的小分子进行药理学靶向。文献检索显示，探索KMT2A重排AML分子发病机制的实验研究以及评估新诱导强化治疗和基于Menin抑制剂的靶向治疗开发的临床研究均有显著进展。在本综述文章中，我们总结了目前对KMT2A在AML发生中生物学的理解，以及通过新化疗方案和使用Menin抑制剂的靶向治疗在KMT2A重排AML治疗中取得的最新持续进展。然而，老年KMT2A重排AML患者的预后仍然较差，可通过包括Menin抑制剂的药物联合研究加以改善。来自正在进行的Menin抑制剂临床试验的许多令人鼓舞的观察结果需要通过随机临床试验加以证实。
Abstract
: Chromosomal rearrangements involving lysine methyltransferase 2A (KMT2A) define a genetically distinct subset of acute myeloid leukemia (AML) in 10% of cases in adult patients; the frequency of is higher in pediatric AML. Translocations involving the locus at chromosome 11q23 result in the formation of a chimeric oncogene partner, where the N-terminal part of is fused to a variety of translocation partners. The leukemogenic activity of -fusion partners is related to their capacity to hyperactivate the expression of and target genes, which stimulate the proliferation of hematopoietic stem cells. The oncogenic activity of fusion proteins requires the binding with Menin, and this interaction can be targeted pharmacologically by small molecules acting as potent and selective Menin inhibitors. : A search of the literature showed a marked development of experimental studies exploring the molecular pathogenesis of AML with and of clinical studies evaluating new induction intensive treatments and the development of a targeted therapy based on Menin inhibitors. : In the present review article, we summarize our current understanding of the biology of in AML development and the recent consistent progress made in the treatment of AML through new chemotherapy regimens and targeted therapy using Menin inhibitors. However, the prognosis of older AML patients remains poor and could be improved by drug combination studies including Menin inhibitors. Many encouraging observations derived from ongoing clinical trials with Menin inhibitors need to be confirmed through randomized clinical trials.
如何引用
AMA
Ugo Testa, Elvira Pelosi, Germana Castelli. Acute Myeloid Leukemias with Alterations of Lysine Methyltransferase 2A (KMT2A): Recent Therapeutic Developments.. Cancers. 2026; doi:10.3390/cancers18091341.
APA
Ugo Testa, Elvira Pelosi, Germana Castelli (2026). Acute Myeloid Leukemias with Alterations of Lysine Methyltransferase 2A (KMT2A): Recent Therapeutic Developments.. Cancers. https://doi.org/10.3390/cancers18091341
GB/T 7714
Ugo Testa, Elvira Pelosi, Germana Castelli. Acute Myeloid Leukemias with Alterations of Lysine Methyltransferase 2A (KMT2A): Recent Therapeutic Developments.[J]. Cancers, 2026 doi:10.3390/cancers18091341.
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