一个由中国香港大学领导的国际研究小组在新一期美国《Science Translational Medicine》杂志上报告，从中药三尖杉属植物中提炼出来的高三尖杉酯碱，在用于治疗携带ＦＬＴ３－ＩＴＤ基因突变的急性髓细胞白血病患者时疗效显著。

急性髓细胞白血病是成年人血液系统常见的癌症，近３０％的急性髓细胞白血病患者携带ＦＬＴ３－ＩＴＤ基因突变。

参与研究的中国香港大学李嘉诚医学院副院长梁如鸿对新华社记者说，标准化疗方法和药物索拉菲尼对携带这种基因突变的急性髓细胞白血病患者的疗效并不理想。为了找出更好的治疗方法，他们利用患者的白血病细胞进行体外药物筛选，发现高三尖杉酯碱对其有显著的抑制作用。

据梁如鸿介绍，高三尖杉酯碱是从三尖杉属植物中提炼出来的生物酯碱。在中国国内，高三尖杉酯碱普遍用于急性髓细胞白血病治疗，但并非针对特定白血病类型，因此疗效并不显著。

梁如鸿等人招募了２４名已复发或难治的携带ＦＬＴ３－ＩＴＤ基因突变的急性髓细胞白血病患者开展临床试验，利用高三尖杉酯碱与索拉菲尼联合治疗，结果有２０名患者体内的白血病细胞被清除，整体存活期显著延长。

梁如鸿说，高三尖杉酯碱可以抑制细胞的蛋白合成，使癌细胞无法制造重要的蛋白，导致癌细胞凋亡。“相对现行的方法，联合治疗的副作用很小，可以应用于体弱或年长的患者，”梁如鸿认为，这项研究为ＦＬＴ３－ＩＴＤ急性髓细胞白血病提供了一种有效的治疗策略。（来源：新华社 林小春）

Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute myeloid leukemia

Abstract  An in vitro drug-screening platform on patient samples was developed and validated to design personalized treatment for relapsed/refractory acute myeloid leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine (HHT), also known as omacetaxine mepesuccinate, exhibited preferential antileukemia effect against AML carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to suppress leukemia growth in vitro and in xenograft mouse models. Mechanistically, the effect was mediated by protein synthesis inhibition and reduction of short-lived proteins, including total and phosphorylated forms of FLT3 and its downstream signaling proteins. A phase 2 clinical trial of sorafenib and HHT combination treatment in FLT3-ITD AML patients resulted in complete remission (true or with insufficient hematological recovery) in 20 of 24 patients (83.3%), reduction of ITD allelic burden, and median leukemia-free and overall survivals of 12 and 33 weeks. The regimen has successfully bridged five patients to allogeneic hematopoietic stem cell transplantation and was well tolerated in patients unfit for conventional chemotherapy, including elderly and heavily pretreated patients. This study validated the principle and clinical relevance of in vitro drug testing and identified an improved treatment for FLT3-ITD AML. The results provided the foundation for phase 2/3 clinical trials to ascertain the clinical efficacy of FLT3 inhibitors and HHT in combination.

原文链接：http://stm.sciencemag.org/content/8/359/359ra129