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急性髓系白血病表观遗传靶点的系统评价

Systematic review of epigenetic targets in acute myeloid leukemia.

作者信息

Verma Shweta, Dhanda Himanshu, Singh Amitabh, Rishi Bhavika, Tanwar Pranay, Chaudhry Sumita, Siraj Fouzia, Misra Aroonima

机构信息

M.Sc Trainee, ICMR-National Institute of Pathology, Safdarjung Hospital Campus Ansari Nagar, New Delhi, India.

Department of Pediatrics, VMMC and Safdarjung Hospital Ansari Nagar, New Delhi, India.

出版信息

Am J Blood Res. 2021 Oct 15;11(5):458-471. eCollection 2021.

Abstract

Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal modalities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy.

摘要

急性髓系白血病(AML)虽然在基因和形态上与其他B细胞和T细胞急性淋巴细胞白血病亚型不同,但却是病程进展最快、预后最差的疾病之一。目前AML的诊断分类虽具有最佳的治愈意图,但治疗结果通常并非治疗开始时所期望的那样。这部分归因于白血病发生的复杂机制以及对化疗的耐药性。耐药的潜在遗传机制与疾病的发病机制一样复杂。耐药AML治疗的最新进展突出了表观遗传靶点的作用。美国食品药品监督管理局(FDA)批准的新靶向疗法也在临床试验中为改善治疗结果提供了一些证据。本综述详细回顾了FDA批准的靶点以及针对CRISPER、嵌合抗原受体T细胞(CAR-T)和其他肠道模式靶向表观遗传靶点的正在进行的临床试验。然而,这组表观遗传靶向疗法需要更多验证以证明其临床疗效。对所有已发表的关于这些靶点、研究药物和FDA批准的靶向疗法的研究进行系统综述总结了这一证据。它还带我们简要回顾了作用机制和治疗靶点。

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