Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients
Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients
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DOI：
10.1038/modpathol.2012.88
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发表时间：
2012-10-01
期刊：
影响因子：
7.5
通讯作者：
Zuo, Zhuang
中科院分区：
文献类型：
--
作者：
Warren, Mikako;Luthra, Rajyalakshmi;Zuo, Zhuang
FMS样酪氨酸激酶3(Flt3)是急性髓系白血病中最常见的突变基因之一，与临床预后密切相关。在疾病过程中可能会发生Flt3突变状态的变化，但这种变化的临床影响尚不清楚。我们回顾了2002年5月至2011年1月期间在我们机构接受Flt3突变评估的3555名急性髓系白血病患者。我们发现，在680例Flt3突变患者中，42例(6.2%)经历了Flt3突变状态的改变。总共有36名初诊时野生型Flt3患者获得突变(阴性/阳性)，6名最初突变的Flt3患者在随后的复发(阳性/阴性)中成为野生型。这些患者的5年生存率与持续野生型Flt3患者相似(阴性/阴性；P=0.464)，但明显好于病程中稳定突变的患者(阳性/阳性；P<；0.001)。然而，在阴性/阳性组中检测到突变后，这些患者的远期存活率与阳性/阳性组复发后的远期存活率一致(P=0.761)。此外，我们没有发现内部串联重复的患者和那些在Flt3基因的酪氨酸激酶域发生点突变的患者之间的存活率有显著差异。这些结果表明，Flt3突变是不稳定的，持续监测Flt3突变状态具有潜在的临床价值。《现代病理学》(2012年)25期，1405年-1412年；doi：10.1038/modpathol.2012.88；2012年6月8日在线发布
FMS-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in acute myeloid leukemia and is associated with worse clinical outcome. Changes in FLT3 mutation status can occur during the course of disease, but the clinical impact of a change is unclear. We retrospectively reviewed 3555 acute myeloid leukemia patients, who have been assessed for FLT3 mutation at our institution between May 2002 and January 2011. We found that 42 (6.2%) out of 680 patients with FLT3 mutation experienced a change of FLT3 mutation status. In all, 36 patients with wild-type FLT3 at the time of initial diagnosis gained mutation (Negative/Positive) and six initially FLT3-mutated patients became wild type during their following relapses (Positive/Negative). The 5-year survival of these patients was similar to that of patients with persistently wild-type FLT3 (Negative/Negative; P = 0.464), and significantly better than patients who had stable FLT3 mutation during their disease course (Positive/Positive; P < 0.001). However, after mutations became detectable in the Negative/Positive group, the forward survival of these patients tracked that of the Positive/Positive group after relapse (P = 0.761). In addition, we did not find a significant difference in survival between patients with internal tandem duplications and those with point mutations in the tyrosine kinase domain of the FLT3 gene. These results suggest that FLT3 mutations are unstable and that there is potential clinical value in continuously monitoring FLT3 mutation status. Modern Pathology (2012) 25, 1405-1412; doi: 10.1038/modpathol.2012.88; published online 8 June 2012