Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML
Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML
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DOI：
10.1182/blood-2009-09-241075
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发表时间：
2010-03-25
期刊：
影响因子：
20.3
通讯作者：
Meshinchi, Soheil
中科院分区：
文献类型：
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作者：
Pollard, Jessica A.;Alonzo, Todd A.;Meshinchi, Soheil
KIT 受体酪氨酸激酶突变是核心结合因子 (CBF) 急性髓系白血病 (AML) 成人患者的预后因素。然而，它们在儿科 CBF AML 中的患病率和预后意义尚未明确。我们对参加 4 个儿科 AML 方案的 203 名 CBF AML 儿科患者的诊断样本进行了 KIT 突变分析（外显子 8 和外显子 17）。 203 份（95% CI，14%-25%）患者样本中的 38 份（19%）检测到 KIT 突变，其中 38 份（95% CI，36%-69%）中的 20 份（52.5%）涉及外显子 8，38 份（95% CI，29%-62%）中的 17 份（45%）涉及外显子 17，1 份（2.5%；29%-62%）涉及外显子 17。 95% CI，0%-14%）涉及两个位置。携带 KIT 突变的患者的 5 年无事件生存率为 55% (+/- 17%)，而野生型 KIT 患者的 5 年无事件生存率为 59% (+/- 9%) (P = .86)。对于有或没有 KIT 突变的患者，完全缓解率、总生存率、无病生存率或复发率没有显着差异。 KIT 突变的定位和细胞遗传学亚型分析 [t(8; 21) 与 inv(16)] 也缺乏预后意义。我们的研究表明，KIT 突变在大量 CBF AML 儿科患者中缺乏预后意义。这一发现与成人系列研究和之前发表的儿科研究不同，可能反映了 CBF AML 治疗方法和/或生物学异质性的差异。本分析中包含的 4 项研究中有两项在 http://clinicaltrials.gov 上注册为 NCT00002798(CCG-2961) 和 NCT00070174 (COG AAML03P1)。 （血。2010；115：2372-2379）
KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8; 21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798(CCG-2961) and NCT00070174 (COG AAML03P1). (Blood. 2010; 115: 2372-2379)