Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Division of Hematology and Oncology, College of Medicine at Chicago, University of Illinois, Chicago, IL, USA.
J Cell Mol Med. 2018 Mar;22(3):1411-1427. doi: 10.1111/jcmm.13478. Epub 2018 Jan 12.
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy. These treatment protocols have remained largely unchanged for the past several decades and only lead to a cure in approximately 30-35% of cases. The advent of targeted therapies in chronic myeloid leukaemia and other malignancies has sparked hope to improve patient outcome in AML. However, the implementation of targeted agents in AML therapy has been unexpectedly cumbersome and remains a difficult task due to a variety of disease- and patient-specific factors. In this review, we describe current standard and investigational therapeutic strategies with a focus on targeted agents and highlight potential tools that might facilitate the development of targeted therapies for this fatal disease. The classes of agents described in this review include constitutively activated signalling pathway inhibitors, surface receptor targets, epigenetic modifiers, drugs targeting the interaction of the hematopoietic progenitor cell with the stroma and drugs that target the apoptotic machinery. The clinical context and outcome with these agents will be examined to gain insight about their optimal utilization.
急性髓系白血病（AML）是一种恶性的髓系血液系统疾病，其特征为造血前体细胞分化障碍和增殖过度。最近的技术进步使我们对 AML 的生物学特性有了更深入的了解，但也揭示了该疾病在细胞遗传学和分子水平上存在巨大的异质性。尽管存在这种异质性，但 AML 的治疗主要采用“一刀切”的方法，包括强化、高毒性的诱导和巩固化疗。这些治疗方案在过去几十年中基本没有改变，只有约 30-35%的病例能够治愈。靶向治疗在慢性髓系白血病和其他恶性肿瘤中的应用，为改善 AML 患者的预后带来了希望。然而，靶向药物在 AML 治疗中的应用出乎意料地复杂，由于各种疾病和患者特异性因素，仍然是一项艰巨的任务。在这篇综述中，我们描述了目前 AML 的标准和研究性治疗策略，重点介绍了靶向药物，并强调了可能有助于为这种致命疾病开发靶向治疗的潜在工具。本综述中描述的药物类别包括持续激活的信号通路抑制剂、表面受体靶点、表观遗传修饰剂、靶向造血祖细胞与基质相互作用的药物以及靶向细胞凋亡机制的药物。我们将研究这些药物的临床背景和结果，以了解其最佳应用。
