IDH1 R132 突变和 IDH1 单核苷酸多态性在核型正常的急性髓系白血病中的影响：SNP rs11554137 是一个不良预后因素。

Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor.

机构信息

Department of Hematology, Hannover Medical School, Carl-Neuberg Str 1, 30625 Hannover, Germany.

出版信息

J Clin Oncol. 2010 May 10;28(14):2356-64. doi: 10.1200/JCO.2009.27.6899. Epub 2010 Apr 5.

DOI:10.1200/JCO.2009.27.6899

PMID:20368538

Abstract

PURPOSE

We 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 METHODS

IDH1 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.

RESULTS

IDH1 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.

CONCLUSION

IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML.

摘要

目的

我们评估了 IDH1 R132 突变和 IDH1 基因同一外显子中已知单核苷酸多态性（SNP）在其他预后标志物背景下对核型正常急性髓系白血病（CN-AML）患者的预后影响。

患者和方法

在两个后续的 AML 多中心治疗试验和 120 名健康志愿者中，直接对 275 名 CN-AML 患者的 IDH1 外显子四进行了测序。此外，还分析了 NPM1、FLT3、CEBPA 和 WT1 的突变，并定量了 IDH1 的 mRNA 表达。

结果

在 10.9%的 CN-AML 患者中发现了 IDH1 R132 突变。在 12%的 CN-AML 患者和 11.7%的健康志愿者中发现了 IDH1 SNP rs11554137。IDH1 R132 突变对预后没有影响。相比之下，在单变量和多变量分析中，IDH1 SNP rs11554137 是总生存的不良预后因素。其他重要因素是年龄、NPM1/FLT3 突变状态、WT1 SNP rs16754 和血小板计数。在 NPM1/FLT3 高危患者（NPM1 野生型或 FLT3 内部串联重复阳性）中，IDH1 SNP rs11554137 的影响最为显著。携带 IDH1 SNP rs11554137 的患者的 IDH1 mRNA 表达高于携带两个野生型等位基因的患者。