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中美科学家新发现有望为血液系统肿瘤治疗带来新突破

2018年09月11日 23:21来源:网络整理手机版

由中国医学科学院血液病医院(血液学研究所)、实验血液学国家重点实验室肖志坚教授和该实验室特聘教授、美国辛辛那提儿童医院医学中心肿瘤生物学家黄刚教授共同带领的科研团队经过七年研究,揭示了低氧诱导因子α(HIF1A)是骨髓增生异常综合征(MDS)发生的关键分子,千龙电影网,这一重大发现有望给这一恶性血液系统肿瘤的治疗带来突破。

该研究成果近日在线发表在国际肿瘤领域顶尖杂志Cancer Discovery。

骨髓增生异常综合征是一种最常见血液系统恶性肿瘤,是由于造血干细胞发生基因突变后出现造血细胞发育异常所致的髓系肿瘤,主要发生于老年人群。30%左右的患者会发展为白血病,被称为白血病前期。现今常规治疗手段无法治愈,是难以攻克的疑难肿瘤之一。

肖志坚说,通过2代测序技术在骨髓增生异常综合征患者中共发现有40-60个基因突变,但对这些基因突变如何导致骨髓增生异常综合征却知之甚少。不同基因突变是否有一个共同发挥作用的因子存在呢?在这个大胆设想的引导下,科研团队通过转录组学和表观基因组学分析,在带有不同基因突变的骨髓增生异常综合征患者的骨髓细胞中发现一种叫做低氧诱导因子α(HIF1A)为一共同作用分子,影响了其信号通路下游的代谢和免疫效应分子,从而导致了造血细胞癌变。

随后,课题组在携带不同骨髓增生异常综合征常见基因突变的转基因小鼠模型研究中,进一步证实了HIF1A功能异常在MDS发生中发挥着核心作用,并且通过基因敲除HIF1A基因或者是应用HIF1A抑制剂,都能逆转转基因小鼠模型的骨髓增生异常综合征的相关临床表征,这些研究结果表明以HIF1A为靶点的治疗有望成为骨髓增生异常综合征患者新的治疗策略。

肖志坚表示,目前大多数的HIF1A小分子抑制物不适用于骨髓增生异常综合征患者,板报网,研发HIF1A特异性靶向药物将是他们接下来主攻的新课题。(记者 张建新)

(责编:龚茜(实习生)、刘洁妍)

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