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用于快速确定急性白血病风险的17基因干度得分

Stanley W K Ng¹, Amanda Mitchell², James A Kennedy^2,3,4

¹Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 1A1, Canada.

|December 8, 2016

概括

一个新的17基因白血病干细胞评分 (LSC17) 可以预测急性髓性白血病 (AML) 患者的治疗耐药性和复发. 这种生物标志物可以识别那些可能无法从标准疗法中获益的高风险个体,指导新型临床试验的招生.

科学领域:

癌症学
分子生物学
生物标志物发现

背景情况:

在治疗急性骨髓性白血病 (AML) 时,对诱导化疗的耐药性和复发是主要的挑战.
目前的风险分层依赖于细胞遗传和分子异常,但有些患者缺乏不良因素,但仍然复发.
白血病干细胞 (LSCs) 由于干细胞的静止性而导致治疗耐药性和复发.

研究的目的:

开发与干性相关的急性髓性白血病 (AML) 的预测和预后生物标志物.
识别高风险AML患者,他们可能对标准诱导化疗没有反应.
为评估新型治疗策略的临床试验提供更好的患者分层.

主要方法:

来自AML患者的LSC+和LSC-细胞分数之间的基因表达差异分析.
对LSC基因表达与生存数据进行稀疏回归分析.
在独立患者队列中验证17基因白血病干细胞评分 (LSC17).

主要成果:

从基因表达数据中生成了17基因白血病干细胞评分 (LSC17).
在各种AML亚型 (n=908) 中,LSC17得分显示出高预后值.
即使在异性干细胞移植后,LSC17也准确地预测了初始治疗耐药性,并确定了表现不佳的患者.

结论:

LSC17评分是一个强大的工具,用于识别预后不佳且对标准治疗有抗性的AML患者.
这种生物标志物可以指导高风险患者参加临床试验,以获得新的预先或后缓解策略.
在急性髓性白血病中,LSC17得分有助于个性化治疗方法.

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