Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital Munich, and Institute of Medical Statistics, Biometry, and Epidemiology, University of Munich, Munich, Germany.
Blood. 2012 May 10;119(19):4383-6. doi: 10.1182/blood-2010-12-327072. Epub 2012 Feb 28.
The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level--measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML.
FLT3 内部串联重复（FLT3ITD）对急性髓系白血病（AML）患者预后的影响取决于突变型与野生型等位基因的比例。在 648 例核型正常（NK）AML 患者中，我们发现定量 FLT3ITD mRNA 水平（表示为（FLT3ITD/wtFLT3）/（FLT3ITD/wtFLT3+1））对预后有显著的独立影响。此外，在 329 例存在 NPM1 基因突变（NPM1+）的患者中可以明显看到这种影响，而在 319 例无 NPM1 突变（wtNPM1）的患者中则没有。在多变量 Cox 回归模型中，定量 FLT3ITD mRNA 水平仅在 NPM1+亚组中对总生存（OS）和无复发生存（RFS）具有独立的预后影响（OS：危险比，5.9；[95%置信区间 [CI]：3.1-11.2]；RFS：危险比，7.5 [95% CI：3.4-16.5]）。FLT3ITD mRNA 水平有助于复发风险分层，并可能有助于指导 NPM1 突变 AML 的缓解后治疗。
