[异柠檬酸脱氢酶基因突变的成人急性髓系白血病的临床特征]

[Clinical characteristics in adult acute myeloid leukemia with isocitrate dehydrogenase gene mutation].

作者信息

Wang Rong-xian, Wu De-pei, Chen Su-ning, He Jun, Xu Yang, Wang Xiu-li, Yin Jia, Tian Hong, Tian Xiao-peng, Sun Ai-ning

机构信息

Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2013 Mar 12;93(10):751-5.

DOI:

PMID:23755812

Abstract

OBJECTIVE

To explore the prevalence and clinical characteristics of isocitrate dehydrogenase (IDH)1 R132 and IDH2 R140/R172 gene mutations in acute myeloid leukemia (AML) patients.

METHODS

Polymerase chain reaction (PCR) and direct sequencing were used to sequence exon 4 of IDH gene in 570 AML patients from 2005 to 2011.

RESULTS

In a cohort of 570 patients, AML IDH gene mutation was found in 90 (15.79%) patients. IDH1 and IDH2 mutations were detected in 27 (4.74%) patients and 63 (11.05%) patients respectively. None of them had the combined mutations of IDH1 and IDH2. The highest frequency of IDH mutations was found in AML M1 (according to the FAB scheme) compared with all other subtypes (P < 0.01). The median age was 53 years in mutated group versus 40 years in wild-type group (P = 0.010). Mutated and wild-type groups had no significant difference in gender, white blood cell count at diagnosis, hemoglobin count and bone marrow blast percentage, excepting for blood platelets level (median 52×10(9)/L vs 31×10(9)/L, P < 0.01). IDH gene mutations were associated with cytogenetically normal (CN)-AML, NPM1 mutations and particularly with the genotype of mutated NPM1 without FLT3-ITD. IDH gene mutations had no significant correlation with WT1, FLT3-TKD and MLL-PTD mutations. IDH mutated patients had a lower complete remission rate than unmutated in non-M3 patients (58.1% vs 77.9%, P < 0.05). And the patients with mutant IDH gene were associated with a shorter overall survival (28.4% vs 51.3%, P < 0.01).

CONCLUSION

IDH gene mutations are more prevalent in elder AML patients and it may constitute a molecular marker for a poor prognosis in AML.

摘要

目的

探讨急性髓系白血病（AML）患者异柠檬酸脱氢酶（IDH）1基因R132位点及IDH2基因R140/R172位点突变的发生率及临床特征。

方法

采用聚合酶链反应（PCR）及直接测序法对2005年至2011年期间收治的570例AML患者的IDH基因第4外显子进行测序。

结果

在570例患者中，90例（15.79%）患者存在AML IDH基因突变。其中，IDH1基因突变27例（4.74%），IDH2基因突变63例（11.05%）。无IDH1与IDH2基因联合突变病例。与其他所有亚型相比，AML M1型（按照FAB分型）中IDH基因突变频率最高（P < 0.01）。突变组患者中位年龄为53岁，野生型组为40岁（P = 0.010）。除血小板水平外（中位数52×10⁹/L对31×10⁹/L，P < 0.01），突变组与野生型组在性别、诊断时白细胞计数、血红蛋白计数及骨髓原始细胞比例方面无显著差异。IDH基因突变与细胞遗传学正常（CN）-AML、NPM1基因突变相关，尤其与无FLT3-ITD的NPM1基因突变型相关。IDH基因突变与WT1、FLT3-TKD及MLL-PTD基因突变无显著相关性。在非M3型患者中，IDH基因突变患者的完全缓解率低于未突变患者（58.1%对77.9%，P < 0.05）。且IDH基因突变患者总生存期较短（28.4%对51.3%，P < 0.01）。