Department of Haematology, Haemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Br J Haematol. 2012 Jul;158(2):208-215. doi: 10.1111/j.1365-2141.2012.09144.x. Epub 2012 May 9.
In acute myeloid leukaemia with normal karyotype (CN-AML), gene mutations (e.g. NPM1, FLT3, CEBPA) as well as deregulated gene expression affect outcome. High expression of ID1 was described as a negative prognostic factor. We have shown that CEBPA regulates ID1 expression. Therefore, we analysed the prognostic impact of ID1 expression in 269 patients (aged 16-60 years) with CN-AML in the context of other molecular markers, particularly CEBPA mutations. ID1(high) status was an independent negative prognostic factor for overall survival (OS) in multivariate analysis when analysed together with age, extramedullary disease, platelets, expression of BAALC and WT1, FLT3-internal tandem duplication, NPM1, WT1 single nucleotide polymorphism rs16754 and IDH1. ID1 expression was higher in CEBPA wildtype patients than in patients with monoallelic CEBPA mutations and these patients showed higher ID1 expression compared to patients with biallelic CEBPA mutations. Thus, when CEBPA mutations were considered, ID1 expression lost its prognostic impact. Likewise, the negative impact of ID1(high) status on relapse-free survival (RFS) was lost when CEBPA mutations were included in the analysis. In CEBPA wildtype patients, ID1 expression had no impact on complete remission-rate, OS or RFS. In conclusion, CEBPA mutations seem to deregulate ID1 expression. Therefore, ID1 expression is not an independent prognostic factor in CN-AML.
在核型正常的急性髓系白血病(CN-AML)中,基因突变(如 NPM1、FLT3、CEBPA)和基因表达失调会影响预后。ID1 的高表达被描述为一个负预后因素。我们已经表明,CEBPA 调节 ID1 的表达。因此,我们分析了 269 例 CN-AML 患者(年龄 16-60 岁)中 ID1 表达与其他分子标志物(特别是 CEBPA 突变)的相关性及其预后影响。在多变量分析中,当与年龄、髓外疾病、血小板、BAALC 和 WT1 的表达、FLT3 内串联重复、NPM1、WT1 单核苷酸多态性 rs16754 和 IDH1 一起分析时,ID1(高)状态是总生存期(OS)的独立负预后因素。ID1 表达在 CEBPA 野生型患者中高于单等位基因突变患者,而这些患者的 ID1 表达高于双等位基因突变患者。因此,当考虑 CEBPA 突变时,ID1 表达失去了其预后意义。同样,当将 CEBPA 突变纳入分析时,ID1(高)状态对无复发生存率(RFS)的负面影响也消失了。在 CEBPA 野生型患者中,ID1 表达对完全缓解率、OS 或 RFS 没有影响。总之,CEBPA 突变似乎会使 ID1 表达失调。因此,ID1 表达不是 CN-AML 的独立预后因素。