Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia
Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia
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DOI：
10.1182/blood-2011-05-353185
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发表时间：
2011-11-24
期刊：
影响因子：
20.3
通讯作者：
Ehrencrona, Hans
中科院分区：
文献类型：
--
作者：
Staffas, Anna;Kanduri, Meena;Ehrencrona, Hans
Flt3、NPM1、CEBPA和WT1基因的突变状态以及ERG、MN1、BAALC、Flt3和WT1基因的表达水平可能是急性髓系白血病(AML)的预后标志。我们在北欧儿童血液与肿瘤学学会(NOPHO)1993或NOPHO 2004方案中登记的儿童AML患者中，对这些遗传标记进行了全面的预后评估。分别分析185例和149例患者的突变状态和表达水平。存在Flt3内部串联复制(ITD)与显著较低的无事件生存率(EFS)相关，而在不存在Flt3-ITD的情况下存在NPM1突变与显著改善EFS相关。此外，高水平的ERG和BAALC转录本与较差的EFS相关。未发现CEBPA和WT1基因突变或MN1、Flt3和WT1基因表达水平与生存率显著相关。在多因素分析中，Flt3-ITD的存在和BAALC的高表达被确定为下层EFS的独立预后标志。我们的结论是，在诊断时分析Flt3和NPM1的突变状态对于儿童AML患者的预后分层很重要，而BAALC基因表达水平的测定可以增加有价值的信息。(血。2011年；118(22)：5905-5913)
Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information. (Blood. 2011;118(22):5905-5913)