State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai, China.
Blood. 2011 Nov 17;118(20):5593-603. doi: 10.1182/blood-2011-03-343988. Epub 2011 Aug 31.
To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)-ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.
为了评估基因突变对急性髓系白血病（AML）患者的预后价值，我们检查了基因状态，包括融合产物，如 AML1（CBFα）-ETO、CBFβ-MYH11、PML-RARα 和染色体易位导致的 MLL 重排，以及基因突变，包括 FLT3、C-KIT、N-RAS、NPM1、CEBPA、WT1、ASXL1、DNMT3A、MLL、IDH1、IDH2 和 TET2，在 1185 例 AML 患者中。临床分析主要在 605 例除 11q23 外无可识别核型异常的患者中进行。在这 605 例患者中，发现 452 例（74.7%）至少有 1 种突变，并研究了基因突变与临床结局的关系。我们揭示了 NPM1、DNMT3A、FLT3、IDH1、IDH2、CEBPA 和 TET2 突变之间的相关性模式。多变量分析确定 DNMT3A 和 MLL 突变是预测总生存期（OS）和无事件生存期（EFS）不良的独立因素，而双等位 CEBPA 突变或无 DNMT3A 突变的 NPM1 突变在整个组和年龄<60 岁的年轻患者中均能改善 OS 和 EFS。分子标志物的使用使我们能够将 605 例患者的系列分为具有潜在临床相关性的不同预后组。
