Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL):: a retrospective study from the European APL Group
Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL):: a retrospective study from the European APL Group
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DOI：
10.1038/sj.leu.2403790
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发表时间：
2005-07-01
期刊：
影响因子：
11.4
通讯作者：
Dombret, H
中科院分区：
文献类型：
--
作者：
Callens, C;Chevret, S;Dombret, H
在大约35%的APL病例中观察到FLT3基因的内部串联重复（ITDs）。如果FLT3-ITD在急性髓性白血病（AML）患者中通常与较差的预后相关，那么其在急性早幼粒细胞白血病（APL）中的预后价值仍存在争议。我们调查了119例APL患者FLT3-ITD的发病率、相关临床特征和预后意义，以及FLT3-D835点突变和N-Ras或K-Ras突变，所有这些患者都前瞻性地纳入了两项连续的APL-93和APL-2000试验。FLT3-ITD、FLT3-D835和Ras的突变发生率分别为38%、20%和4%。FLT3-ITD的存在与高白细胞计数、高Sanz指数、m3变异亚型和V/ S PML- RAR α亚型相关。完全缓解（CR）、诱导死亡和CR死亡率不受FLT3或Ras突变以及累积复发率的影响。然而，FLT3-ITD患者的总生存期较短（P = 0.09），因为复发后生存期非常差（P = 0.02）。这一特征在AML患者中也有报道，表明FLT3-ITD患者存在潜在的遗传不稳定性，导致复发时获得其他未知的不良预后基因突变。
Internal tandem duplications (ITDs) of the FLT3 gene have been observed in about 35% of APL cases. If FLT3-ITD is associated with a worse outcome in patients with acute myeloid leukemia (AML) in general, its prognostic value in acute promyelocytic leukemia (APL) is still a matter of debate. We investigated incidence, associated clinical features, and prognostic implication of FLT3-ITD, but also FLT3-D835 point mutation and N-Ras or K-Ras mutations in 119 APL patients, all prospectively enrolled in the two consecutive APL-93 and APL-2000 trials. Mutation incidences were 38, 20, and 4%, for FLT3-ITD, FLT3-D835, and Ras, respectively. The presence of FLT3-ITD was associated with high white blood cell count, high Sanz index, M3-variant subtype, and V/ S PML- RAR alpha isoforms. Complete remission (CR), induction death, and death in CR rates were not affected by FLT3 or Ras mutations, as well as cumulative incidence of relapse. However, a trend for a shorter overall survival (P = 0.09) was observed in FLT3-ITD patients, because of a very poor postrelapse survival (P = 0.02). This feature, which has been also reported in patients with AML in general, is suggestive of an underlying genetic instability in FLT3-ITD patients, leading to the acquisition of additional unknown bad-prognosis gene mutations at relapse.