Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors
Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors
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DOI：
10.1182/blood-2016-03-705053
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发表时间：
2016-06-16
期刊：
影响因子：
20.3
通讯作者：
Sauvageau, Guy
中科院分区：
文献类型：
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作者：
Lavallee, Vincent-Philippe;Krosl, Jana;Sauvageau, Guy
在这项研究中，我们分析了14个样本的RNA测序数据，其特征在于双等位基因CEBPA（双）突变包括在Leucegene收集的415个原发性急性髓细胞白血病（AML）标本，并首次描述了高频率复发突变的粒细胞集落刺激因子受体基因CSF 3R，通过JAK-STAT蛋白质的信号。这些原始人类样本的化学询问显示，无论其CSF 3R突变状态如何，对所有JAK抑制剂的敏感性均一致且特异，表明该白血病亚组中JAK-STAT信号传导的一般致敏性。总之，这些结果确定了CSF 3R和CEBPA突变在一个明确定义的AML亚组中的共同发生，这对JAK抑制剂有一致的反应，并为这种疾病的个性化临床试验铺平了道路。
In this study, we analyzed RNA-sequencing data of 14 samples characterized by biallelic CEBPA (CEBPA(bi)) mutations included in the Leucegene collection of 415 primary acute myeloid leukemia (AML) specimens, and describe for the first time high frequency recurrent mutations in the granulocyte colony-stimulating factor receptor gene CSF3R, which signals through JAK-STAT proteins. Chemical interrogation of these primary human specimens revealed a uniform and specific sensitivity to all JAK inhibitors tested irrespective of their CSF3R mutation status, indicating a general sensitization of JAK-STAT signaling in this leukemia subset. Altogether, these results identified the co-occurrence of mutations in CSF3R and CEBPA in a well-defined AML subset, which uniformly responds to JAK inhibitors and paves the way to personalized clinical trials for this disease.