Acute myeloid leukemia ontogeny is defined by distinct somatic mutations
Acute myeloid leukemia ontogeny is defined by distinct somatic mutations
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DOI：
10.1182/blood-2014-11-610543
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发表时间：
2015-02-26
期刊：
影响因子：
20.3
通讯作者：
Ebert, Benjamin L.
中科院分区：
文献类型：
--
作者：
Lindsley, R. Coleman;Mar, Brenton G.;Ebert, Benjamin L.
急性髓性白血病（AML）可在既往髓性恶性肿瘤（继发性AML [s-AML]）、致白血病治疗（治疗相关AML [t-AML]）后或无可识别前驱症状或已知暴露（新发AML）的情况下发生。AML发展的这些不同途径的遗传基础尚未确定。我们对194例严格定义的s-AML或t-AML患者和105例AML患者进行了靶向突变分析。SRSF 2、SF 3B 1、U2 AF 1、ZRSR 2、ASXL 1、EZH 2、BCOR或STAG 2中突变的存在对于s-AML诊断的特异性>95%。对个体患者的系列样本的分析显示，这些突变发生在白血病发生的早期，并且经常在克隆缓解中持续存在。在t-AML和老年初治AML人群中，这些改变定义了一种独特的遗传亚型，与临床确诊的s-AML具有相同的临床病理学特征，并突出显示了一部分临床结局较差的患者，包括完全缓解率较低、复发频率较高和无事件生存期缩短。该试验在www.clinicaltrials.gov上注册为#NCT 00715637。
Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637.