从骨髓增生异常综合征（MDS）转化为急性髓系白血病（AML）时可检测到的FLT3内部串联重复（FLT3-ITD）或RAS突变预示预后极差。
Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes.
作者信息
Badar Talha, Patel Keyur P, Thompson Philip A, DiNardo Courtney, Takahashi Koichi, Cabrero Monica, Borthakur Gautam, Cortes Jorge, Konopleva Marina, Kadia Tapan, Bohannan Zach, Pierce Sherry, Jabbour Elias J, Ravandi Farhad, Daver Naval, Luthra Raja, Kantarjian Hagop, Garcia-Manero Guillermo
机构信息
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Leuk Res. 2015 Dec;39(12):1367-74. doi: 10.1016/j.leukres.2015.10.005. Epub 2015 Oct 19.
BACKGROUND
The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes.
METHODS
We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages.
RESULTS
We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p<0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.
背景
驱动骨髓增生异常综合征（MDS）向急性髓系白血病（AML）转化的分子事件尚未完全明确。我们推测在MDS向AML转化时检测到这些突变可能导致较差的预后。
方法
我们分析了2004年至2013年间入住我院的102例MDS患者，这些患者诊断时为野生型（wt）FLT3-ITD和RAS，进展为AML，并且在MDS和AML阶段均进行了系列突变检测。
结果
在转化为AML时，我们在27例（26%）患者中检测到FLT3-ITD和/或RAS突变。22例（81%）患者有RAS突变，5例（19%）有FLT3-ITD突变。检测到RAS和/或FLT3-ITD突变的患者白血病转化后的中位生存期为2.4个月，而保留wt RAS和FLT3-ITD的患者为7.5个月（风险比[HR]：3.08，95%置信区间[CI]：1.9 - 5.0，p<0.0001）。在多变量分析中，FLT3-ITD和RAS突变对不良预后具有独立的预后意义。
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