Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes.
Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes.
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ASXL1和TP53突变在与骨髓增生相关的急性髓样白血病的分子分类和预后中的作用。
DOI：
10.18632/oncotarget.3460
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发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Birnbaum D
中科院分区：
文献类型：
--
作者：
Devillier R;Mansat-De Mas V;Gelsi-Boyer V;Demur C;Murati A;Corre J;Prebet T;Bertoli S;Brecqueville M;Arnoulet C;Recher C;Vey N;Mozziconacci MJ;Delabesse E;Birnbaum D
急性髓性白血病（AML）伴骨髓增生异常相关变化（AML-MRC）定义为存在多系发育异常（MLD）和/或骨髓增生异常综合征（MDS）相关细胞遗传学和/或既往MDS。本研究的目的是根据MLD的存在、细胞遗传学和结果，在125例AML-MRC患者中基于ASXL 1、RUNX 1、DNMT 3A、NPM 1、FLT 3和TP 53的突变确定不同的生物学和预后亚组。ASXL 1突变（n=26，21%）与较高比例的骨髓粒细胞生成障碍相关（突变型vs野生型：75% vs 55%，p=0.030），并且主要见于中度细胞遗传学AML（23/26），其中它们预测的2年总生存率较低（OS，突变型vs野生型：14% vs 37%，p=0.030）。TP 53突变（n=28，22%）主要见于复杂核型AML（26/28），并预测不利细胞遗传学风险AML的不良结局（突变型vs野生型：9% vs 40%，p=0.040）。在多变量分析中，ASXL 1或TP 53突变的存在是与较短OS相关的唯一独立因素（HR，95%CI：2.53，1.40-4.60，p=0.002），而MLD、MDS相关细胞遗传学和既往MDS病史不影响OS。我们得出结论，ASXL 1和TP 53突变在AML-MRC中鉴定了两个分子亚组，具有特定的不良预后。这可能有助于未来的诊断和预后分类。
Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications.
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作者：
Vardiman, James W.;Thiele, Juergen;Bloomfield, Clara D.
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10.1
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