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Leukemia. 2019 Oct 23. doi: 10.1038/s41375-019-0604-8. [Epub ahead of print]

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

Author information

1
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
2
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
3
Department of Acute and Tertiary Care, University of Tennessee Health Science Center, Memphis, TN, USA.
4
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
5
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
6
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
7
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA. jlamba@cop.ufl.edu.

Abstract

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.

PMID:
31645648
DOI:
10.1038/s41375-019-0604-8

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