Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21):: A Cancer and Leukemia Group B study
Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21):: A Cancer and Leukemia Group B study
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DOI：
10.1200/jco.2006.06.9500
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发表时间：
2006-08-20
影响因子：
45.3
通讯作者：
Bloomfield, Clara D.
中科院分区：
文献类型：
--
作者：
Paschka, Peter;Marcucci, Guido;Bloomfield, Clara D.
目的分析突变型KIT（mutKIT）在核心结合因子（core binding factor，core binding factor）inv（16）（p13 q22）和t（8;21）（q22;q22）急性髓系白血病（acute myeloid leukemia，AML）中的预后影响。21），分配到缓解后治疗组，重复周期使用较高剂量阿糖胞苷，分析外显子17中的mutKIT（mutKIT 17）和8（mutKIT 8）通过变性高效液相色谱和诊断时的直接测序。结果在16例inv患者中，29.5%有mutKIT（16%有mutKIT 17，13%有单一mutKIT 8）。在t（8，21）患者中，22%的患者有mutKIT（18%的患者有mutKIT 17，4%的患者有单一mutKIT 8）。mutKIT和野生型KIT（wtKIT）患者的完全缓解率在两个细胞遗传学组中相似。在inv（16）中，与wtKIT患者相比，mutKIT患者（P= 0.05; 5年CIR，56% v29%）和mutKIT 17患者（P= 0.002; 5年CIR，80% v29%）的累积复发率（CIR）更高。一旦数据根据性别进行调整，mutKIT预测的总生存期（OS）更差。In t（8;结论我们首次报道mutKIT，特别是mutKIT 17，具有较高的复发风险，mutKIT 17和mutKIT 8似乎对inv（1 6）AML患者的OS有不利影响。我们还证实了mutKIT对t（8;21）AML复发风险的不利影响。我们建议，核心结合因子AML患者应在诊断时筛查mutKIT，以实现预后和治疗目的，因为激活的KIT可能被新型酪氨酸激酶抑制剂靶向。
Purpose To analyze the prognostic impact of mutated KIT (mutKIT) in core-binding factor acute myeloid leukemia (AML) with inv(16)(p13q22) and t(8;21)(q22;q22).Patients and Methods Sixty-one adults with inv(16) and 49 adults with t(8;21), assigned to postremission therapy with repetitive cycles of higher dose cytarabine were analyzed for mutKIT in exon 17 (mutKIT17) and 8 (mutKIT8) by denaturing high-performance liquid chromatography and direct sequencing at diagnosis. The median follow-up was 5.3 years.Results Among patients with inv(16), 29.5% had mutKIT (16% with mutKIT17 and 13% with sole mutKIT8). Among patients with t(8,21), 22% had mutKIT(18% with mutKIT17 and 4% with sole mutKIT8). Complete remission rates of patients with mutKIT and wild-type KIT (wtKIT) were similar in both cytogenetic groups. In inv(1 6), the cumulative incidence of relapse (CIR) was higher for patients with mutKIT (P=.05; 5-year CIR, 56% v 29%) and those with mutKIT17 (P=.002; 5-year CIR, 80% v29%) compared with wtKIT patients. Once data were adjusted for sex, mutKIT predicted worse overall survival (OS). In t(8;21), mutKITpredicted higher CIR (P=.017; 5-year CIR, 70% v 36%), but did not influence OS.Conclusion We report for the first time that mutKIT, and particularly mutKIT17, confer higher relapse risk, and both mutKIT17 and mutKIT8 appear to adversely affect OS in AML with inv(1 6). We also confirm the adverse impact of mutKIT on relapse risk in t(8;21) AML. We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors.