A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia
A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia
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DOI：
10.1038/s41375-019-0604-8
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发表时间：
2020-03-01
期刊：
影响因子：
11.4
通讯作者：
Lamba, Jatinder K.
中科院分区：
文献类型：
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作者：
Elsayed, Abdelrahman H.;Rafiee, Roya;Lamba, Jatinder K.
最近，LSCs中丰富的mRNA表达特征被用于创建17基因白血病干细胞(LSC17)评分，以预测成人AML的预后。通过对参加AML02多中心临床试验(NCT00136084)的163名儿童受试者的临床结局和LSC基因表达水平进行Cox-Lasso回归模型拟合，我们得出了对儿童AML有预后价值的6基因LSC评分(PLSC6)。在AML02队列中，低pLSC6组(n=97)患者的5年无事件生存率(EFS)为78.3%(95%CI=70.586.9%)，而高pLSC6组(n=66)患者的5年无事件生存率(EFS)为34.5%(95%CI=24.7-48.2%)，p<；0.00001。在调整了诱导1-MRD状态、风险组、Flt3状态、确诊时WBC计数和年龄后，pLSC6仍然与EFS和总生存期(OS)显著相关。在AML02队列中开发的pLSC6公式在儿科AML-靶项目数据(n=205)中得到验证，证实了其在单预测和多预测Cox回归模型中的预后价值。在这两个队列中，pLSC6预测移植患者的结果，这表明它是移植转诊的有用标准。我们的结果表明，pLSC6评分在重新定义初始风险分层和识别不良风险AML方面有希望，从而为开发新的治疗策略提供指导。
Recently, mRNA-expression signature enriched in LSCs was used to create a 17-gene leukemic stem cell (LSC17) score predictive of prognosis in adult AML. By fitting a Cox-LASSO regression model to the clinical outcome and gene-expression levels of LSC enriched genes in 163 pediatric participants of the AML02 multi-center clinical trial (NCT00136084), we developed a six-gene LSC score of prognostic value in pediatric AML (pLSC6). In the AML02 cohort, the 5-year event-free survival (EFS) of patients within low-pLSC6 group (n = 97) was 78.3 (95% CI = 70.5-86.9%) as compared with 34.5(95% CI = 24.7-48.2 %) in patients within high-pLSC6 group (n = 66 subjects), p < 0.00001. pLSC6 remained significantly associated with EFS and overall survival (OS) after adjusting for induction 1-MRD status, risk-group, FLT3-status, WBC-count at diagnosis and age. pLSC6 formula developed in the AML02 cohort was validated in the pediatric AML-TARGET project data (n = 205), confirming its prognostic value in both single-predictor and multiple-predictor Cox regression models. In both cohorts, pLSC6 predicted outcome of transplant patients, suggesting it as a useful criterion for transplant referrals. Our results suggest that pLSC6 score holds promise in redefining initial risk-stratification and identifying poor risk AML thereby providing guidance for developing novel treatment strategies.