Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Blood. 2011 Oct 27;118(17):4561-6. doi: 10.1182/blood-2011-04-348888. Epub 2011 Aug 26.
IDH1 SNP rs11554137 was recently reported in association with poor prognosis in normal karyotype adult acute myeloid leukemia (AML). We aimed to determine the prevalence, clinical associations, and prognostic significance of SNP rs11554137 in unselected pediatric and adult AML patients. Diagnostic marrow specimens from 527 AML patients treated on the pediatric trial Children's Oncology Group-AAML03P1 (N = 253) or adult SWOG trials (N = 274) were analyzed for the presence of the SNP. SNP rs11554137 was present in 11% of all patients. SNP status had no prognostic impact on survival in pediatric patients. In adult AML, overall survival for SNP-positive patients was 10% versus 18% for SNP-negative patients (P = .44). Among the 142 adults who achieved complete remission, 5-year relapse-free survival was significantly worse for SNP-positive patients (0% vs 25%, P = .0014). However, among adults with normal cytogenetics, FLT3/ITD was present in 90% of SNP-positive patients versus 59% of SNP-negative patients (P = .0053). In multivariate analysis, adjusting for the effects of age, cytogenetics, and FLT3/ITD, the independent prognostic effect of SNP positivity was not statistically significant (hazard ratio = 1.72, P = .18). The clinical profile of SNP-positive patients suggests that SNP rs11554137 may have biologic effects that bear further investigation. The clinical trials in this study are registered at http://www.clinicaltrials.gov as #NCT000707174 and #NCT00899171.
IDH1 SNP rs11554137 最近被报道与正常核型成人急性髓系白血病（AML）的不良预后相关。我们旨在确定 SNP rs11554137 在未选择的儿科和成人 AML 患者中的流行率、临床关联和预后意义。对在儿科试验儿童肿瘤学组-AAML03P1（N=253）或成人 SWOG 试验（N=274）中接受治疗的 527 例 AML 患者的诊断性骨髓标本进行分析，以确定 SNP 的存在。SNP rs11554137 存在于所有患者的 11%中。SNP 状态对儿科患者的生存无预后影响。在成人 AML 中，SNP 阳性患者的总生存为 10%，而 SNP 阴性患者为 18%（P=.44）。在 142 例达到完全缓解的成年人中，SNP 阳性患者的 5 年无复发生存率明显较差（0% vs 25%，P=.0014）。然而，在具有正常细胞遗传学的成年人中，SNP 阳性患者的 FLT3/ITD 阳性率为 90%，而 SNP 阴性患者为 59%（P=.0053）。在多变量分析中，调整年龄、细胞遗传学和 FLT3/ITD 的影响后，SNP 阳性的独立预后影响无统计学意义（危险比=1.72，P=.18）。SNP 阳性患者的临床特征表明，SNP rs11554137 可能具有进一步研究的生物学效应。本研究中的临床试验在 http://www.clinicaltrials.gov 上注册为#NCT000707174 和#NCT00899171。
