Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor
Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor
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DOI：
10.1200/jco.2009.27.6899
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发表时间：
2010-05-10
影响因子：
45.3
通讯作者：
Krauter, Juergen
中科院分区：
文献类型：
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作者：
Wagner, Katharina;Damm, Frederik;Krauter, Juergen
我们评估了IDH1 R132突变和位于IDH1基因同一外显子的已知单核苷酸多态性（SNP）在细胞遗传学正常的急性髓系白血病（CN-AML）患者中的预后影响，并与其他预后标志物进行比较。来自两项后续AML多中心治疗试验的AML患者和120名健康志愿者。结果10.9%的CN-AML患者存在IDH1 R132突变，其中10.9%的CN-AML患者存在IDH1 R132突变。IDH1 SNP rs11554137在12%的CN-AML患者和11.7%的健康志愿者中发现。IDH1 R132突变对预后无影响。相比之下，IDH1 SNP rs11554137在单变量和多变量分析中是总生存率的不良预后因素。其他重要因素包括年龄、NPM1/FLT3突变状态、WT1 SNP rs16754和血小板计数。IDH1 SNP rs11554137的影响在NPM1/FLT3高风险患者（NPM1野生型或FLT3内部串联重复阳性）中最为明显。结论IDH1基因rs11554137突变与CN-AML预后不良相关，而IDH1基因R132突变与CN-AML预后不良无关。
PurposeWe assessed the prognostic impact of IDH1 R132 mutations and a known single nucleotide polymorphism (SNP) located in the same exon of the IDH1 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.Patients and MethodsIDH1 exon four was directly sequenced in 275 CN-AML patients from two subsequent AML multicenter treatment trials and 120 healthy volunteers. Moreover, mutations in NPM1, FLT3, CEBPA, and WT1 were analyzed, and mRNA expression of IDH1 was quantified.ResultsIDH1 R132 mutations were found in 10.9% of CN-AML patients. IDH1 SNP rs11554137 was found in 12% of CN-AML patients and 11.7% of healthy volunteers. IDH1 R132 mutations had no impact on prognosis. In contrast, IDH1 SNP rs11554137 was an adverse prognostic factor for overall survival in univariate and multivariate analysis. Other significant factors were age, NPM1/FLT3 mutational status, WT1 SNP rs16754, and platelet count. The impact of IDH1 SNP rs11554137 was most pronounced in the NPM1/FLT3 high-risk patients (either NPM1 wild-type or FLT3-internal tandem duplication positive). Patients with IDH1 SNP rs11554137 had a higher expression of IDH1 mRNA than patients with two wild-type alleles.ConclusionIDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML.