Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis
Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis
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DOI：
10.1038/sj.leu.2403838
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发表时间：
2005-08-01
期刊：
影响因子：
11.4
通讯作者：
Naoe, T
中科院分区：
文献类型：
--
作者：
Yanada, M;Matsuo, K;Naoe, T
fms样酪氨酸激酶（FLT3）基因畸变的两种不同形式，内部串联重复（ITD）和酪氨酸激酶结构域（TKD）突变，已被确认在相当大比例的急性髓性白血病（AML）患者。为了研究其预后意义，我们对4项已发表的研究进行了荟萃分析，这些研究根据FLT3状态提供了生存信息：ITD、TKD突变和野生型。无病生存期（DFS）的总体风险比为1.88（95%置信区间（CI）1.58 - 2.23; P <0.001），ITD为1.86（95% CI：1.52 - 2.29; P <0.001），TKD为1.90（95% CI：1.40 - 2.60; P <0.001）。总生存率的相应比值分别为1.61（95%CI：1.37 - 1.89; P <0.001）、1.68（95%CI：1.39 - 2.03; P <0.001）和1.37（95%CI：0.94 - 2.01; P = 0.104）。诊断时的白色血细胞计数和细胞遗传学风险分类均不是异质性的重要来源。这些结果表明，FLT3突变对AML的结局具有不良影响，并且TKD突变的负面影响似乎与ITD在DFS方面的负面影响相当。尽管应该记住，这项荟萃分析是基于从观察性研究中提取的数据，但这些结果可能证明根据FLT3状态对AML采取风险适应性治疗策略是合理的。
Two distinct forms of fms-like tyrosine kinase (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, have been recognized in a substantial proportion of patients with acute myeloid leukemia (AML). To investigate their prognostic significance, we performed a meta-analysis of the four published studies that provided survival information according to the FLT3 status: ITD, TKD mutation, and wild type. The summary hazard ratios for disease-free survival (DFS) were 1.88 ( 95% confidence interval (CI) 1.58- 2.23; P < 0.001) for FLT3 mutations, 1.86 (95% CI: 1.52-2.29; P < 0.001) for ITD, and 1.90 (95% CI: 1.40-2.60; P < 0.001) for TKD mutation. The corresponding ratios for overall survival were 1.61 (95% CI: 1.37-1.89; P < 0.001), 1.68 (95% CI: 1.39-2.03; P < 0.001), and 1.37 (95% CI: 0.94-2.01; P=0.104). Neither white blood cell count at diagnosis nor cytogenetic risk category was a significant source of heterogeneity. These findings indicate that FLT3 mutations have an adverse effect on the outcome for AML, and that the negative impact of TKD mutation seems comparable to that of ITD with regard to DFS. Although it should be borne in mind that this meta-analysis was based on data abstracted from observational studies, these results may justify the risk-adapted therapeutic strategies for AML according to the FLT3 status.