A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia

• Published in: Leukemia Vol. 34; no. 3; pp. 735 - 745
• Main Authors: Elsayed, Abdelrahman H., Rafiee, Roya, Cao, Xueyuan, Raimondi, Susana, Downing, James R., Ribeiro, Raul, Fan, Yiping, Gruber, Tanja A., Baker, Sharyn, Klco, Jeffery, Rubnitz, Jeffrey E., Pounds, Stanley, Lamba, Jatinder K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2020; Nature Publishing Group
• Subjects: 38/61; 38/91; 631/67/1990; 692/699/67/1990; Acute myeloid leukemia; Adolescent; Cancer; Cancer Research; Care and treatment; Child; Child, Preschool; Critical Care Medicine; Diagnosis; Disease-Free Survival; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genetic aspects; Genetic research; Health aspects; Hematology; Humans; Infant; Intensive; Internal Medicine; Leukemia; Leukemia in children; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Male; Medical prognosis; Medicine; Medicine & Public Health; Messenger RNA; mRNA; Myeloid leukemia; Oncology; Oncology, Experimental; Patients; Pediatrics; Prognosis; Proportional Hazards Models; Regression Analysis; Regression models; Risk; Risk Assessment; Severity of Illness Index; Stem cells; Survival; Young Adult; United States
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-019-0604-8

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.