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Acute myeloid leukemia

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

Leukemia volume 34, pages 735–745 (2020)Cite this article

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A Correction to this article was published on 16 April 2020

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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.

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Acknowledgements

We gratefully acknowledge funding from ALSAC, University of Florida-Opportunity funds and NIH grant R01-CA132946 (Lamba and Pounds). We thank Dr. Dario Campana and Coustan-Smith for minimal residual disease (MRD) data and Dr. Soheil Meshinchi for insightful comments.

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Authors and Affiliations

  1. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA

    Abdelrahman H. Elsayed, Roya Rafiee & Jatinder K. Lamba

  2. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Xueyuan Cao, Yiping Fan & Stanley Pounds

  3. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Susana Raimondi, James R. Downing, Tanja A. Gruber & Jeffery Klco

  4. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Raul Ribeiro, Tanja A. Gruber & Jeffrey E. Rubnitz

  5. Department of Acute and Tertiary Care, University of Tennessee Health Science Center, Memphis, TN, USA

    Xueyuan Cao

  6. Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA

    Sharyn Baker

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  1. Abdelrahman H. Elsayed
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Contributions

Study concept and design: JKL, AHE, and SP; Acquisition, analysis, and interpretation of data: All authors; Drafting manuscript: JKL, AHE, and SP; Critical revision of manuscript for important intellectual content: All authors; Statistical analysis: SP, XC, AHE, and YF. JKL and SP had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Jatinder K. Lamba.

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The authors declare that they have no conflict of interest.

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This research was supported by NIH R01CA132946 and University of Florida, Opportunity funds.

This work was previously presented in the oral session at 2018 Annual American Society of Hematology meeting, Dec 2018, San Diego, California, USA.

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Elsayed, A.H., Rafiee, R., Cao, X. et al. A six-gene leukemic stem cell score identifies high risk pediatric acute myeloid leukemia. Leukemia 34, 735–745 (2020). https://doi.org/10.1038/s41375-019-0604-8

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