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预测健康人的急性骨髓性白血病风险

By LabMedica International staff writers
Posted on 07 Aug 2018
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图片:一名急性骨髓性白血病患者的血液涂片显示极大的不成熟成髓细胞,它有许多核仁。这些成髓细胞的鲜明特征是红色线状的“Auer小体”,由晶体化颗粒组成(图片蒙犹他大学医学院惠赐)。
图片:一名急性骨髓性白血病患者的血液涂片显示极大的不成熟成髓细胞,它有许多核仁。这些成髓细胞的鲜明特征是红色线状的“Auer小体”,由晶体化颗粒组成(图片蒙犹他大学医学院惠赐)。

急性骨髓性白血病(AML)的发病率随年龄增长而增高,如果65岁后才得到诊断,死亡率超过90%。大多数病例的发生不伴有任何可检测的早期症状,病人通常表现出骨髓衰竭的急性并发症。

 

这类从头AML病例发作前,白血病前期造血干细胞和祖细胞(HSPC)经过克隆,一般会积累体细胞突变。然而,未患AML的健康人衰老过程中HSPC里也会积累AML突变,这种现象被称为年龄相关的克隆造血作用(ARCH)

 

以加拿大安大略省多伦多市玛格丽特公主癌症中心(www.uhn.ca)的科学家为首的一组来自多国的科学家分析了95AML前期病例以及414名年龄与性别相同的对照者的外周血样。AML前期样本于得到诊断的平均6.3年前获得。科研小组用另一队列确证了他们的发现,包括29例病例和262名对照。科研小组用深度测序分析了患AML时反复突变的基因,以分辨AML风险高者与良性ARCH者。

 

科学家报道,AML前期病例不同于对照者,每份样本中有更多突变,等位基因变异的频率更高,说明克隆扩张更强,某些基因的突变更丰富。用基因参数导出的模型能准确预测无AML的存活期。如果把探索组和确证组合在一起,73.4%AML病例有ARCH,而36.7%的对照者有ARCH。两组的DNMTA3ATET2都发生突变。科研小组表示他们没有观察到任何经典的NPM2突变或FLT3内部串联重复突变,他们说这与病程后来出现的这些突变一致。

 

研究人员还发现某些基因里的突变比其它基因里的突变造成更大的AML风险。例如,DNMTA3ATET2里的突变诱发AML的风险不高,而TP53U2F1里的突变导致的疾病恶化风险更高。科学家还调取病人电子病历中的数据,开发了一种预测检验。这种检验能在确诊前612个月预测AML,灵敏度为25.7%,特异性为98.2%

 

该研究的论文发表于201879日的《自然》杂志。资深合著者之一、癌症研究资深研究员George S. Vassiliou博士说:我们希望利用这些成果开发可靠的筛查检验,发现哪些人有风险,并进一步研究如何预防或遏制AML的进展。

Related Links:

玛格丽特公主癌症中心>>> www.uhn.ca


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