急性髓细胞白血病的靶向治疗

Advances in targeted treatment of acute myeloid leukemia

目前，对急性髓细胞白血病（AML）的治疗仍是以化疗为主。酪氨酸激酶抑制剂（TKI）伊马替尼在慢性粒细胞白血病患者的成功应用，加速了TKI肿瘤靶向治疗的研究。随着第2代基因测序技术的出现，相关研究者对AML的基因突变谱有了完整的认识。基于这一基础，研究者们尝试研发小分子靶向药物治疗AML。在近几十年均无针对AML的新药上市背景下，2017年美国食品药品监督管理局（FDA）批准了4种治疗AML的新药，因此2017年亦被称为AML之年。这些新药已被纳入2018年版美国国立综合癌症网（NCCN）指南，并且被纳入AML的一线治疗方案中，从而丰富了AML的治疗方案。除这4种已经获批上市的新药外，还有一系列AML靶向药物处于临床前研究或者临床试验阶段。未来，随着更多新药的上市，AML的治疗将有望真正进入靶向治疗时代，从而实现个体化精准治疗。笔者拟就目前已上市及未来非常有望上市的Fins样酪氨酸激酶（FLT）3抑制剂、异柠檬酸脱氢酶（IDH）抑制剂、B淋巴细胞瘤（BCL）2拮抗剂和免疫毒素等AML靶向治疗药物进行简要阐述。

Chemotherapy is still the main treatment of acute myeloid leukemia （AML） for the moment. The successful use of imatinib in chronic myeloid leukemia has accelerated the study of targeted therapy. With the development of next generation sequencing, researchers have a complete understanding of AML gene mutation profile. Based on that, scientists have tried to develop small molecular targeted drugs. There is no new drug for AML approved for several decades, until the United States Food and Drug Administration （FDA） approved four drugs for AML in 2017. So 2017 can be considered as the year of AML. These new drugs have been recommended in the National Comprehensive Cancer Network （NCCN） guidelines （2018） and have become the first line treatment of AML. In addition to the four approved new drugs, many drugs are in clinical trials or in preclinical stage. When more new drugs are approved in the future, the treatment of AML will truly enter the era of targeted therapy or precision therapy. This article summarizes the AML targeting drugs that have been approved and might be approved in the future, mainly including Fms-like tyrosine kinase （FLT） 3 inhibitors, isocitrate dehydrogenase （IDH） inhibitors, B-cell lymphoma （BCL）2 inhibitors,immunotoxins and so on.