Untargeted metabolomics of newborn dried blood spots reveals sex-specific associations with pediatric acute myeloid leukemia

Lauren Petrick; Partow Imani; Kelsi Perttula; Yukiko Yano; Todd Whitehead; Catherine Metayer; Courtney Schiffman; Georgia Dolios; Sandrine Dudoit; Stephen Rappaport

doi:10.1016/j.leukres.2021.106585

Untargeted metabolomics of newborn dried blood spots reveals sex-specific associations with pediatric acute myeloid leukemia

Leuk Res. 2021 Jul:106:106585. doi: 10.1016/j.leukres.2021.106585. Epub 2021 Apr 24.

Authors

Affiliations

¹ The Institute of Exposomics Research, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Center for Integrative Research on Childhood Leukemia and the Environment, University of California, Berkeley, CA, 94720, USA. Electronic address: lauren.petrick@mssm.edu.
² Division of Biostatistics, School of Public Health, University of California, Berkeley, CA, 94720, USA.
³ Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA; Department of Health Sciences, California State University East Bay, Hayward, CA, 94542, USA.
⁴ Center for Integrative Research on Childhood Leukemia and the Environment, University of California, Berkeley, CA, 94720, USA; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA.
⁵ Center for Integrative Research on Childhood Leukemia and the Environment, University of California, Berkeley, CA, 94720, USA; Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, 94720, USA.
⁶ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁷ Division of Biostatistics, School of Public Health, University of California, Berkeley, CA, 94720, USA; Department of Statistics, University of California, Berkeley, CA, 94720, USA.

Abstract

The etiology of pediatric acute myeloid leukemia (AML) is largely unknown, but evidence for mutations in utero and long latency periods suggests that environmental factors play a role. Therefore, we used untargeted metabolomics of archived newborn dried blood spots (DBS) to investigate neonatal exposures as potential causal risk factors for AML. Untargeted metabolomics profiling was performed on DBS punches from 48 pediatric patients with AML and 46 healthy controls as part of the California Childhood Leukemia Study (CCLS). Because sex disparities are suggested by differences in AML incidence rates, metabolite features associated with AML were identified in analyses stratified by sex. There was no overlap between the 16 predictors of AML in females and 15 predictors in males, suggesting that neonatal metabolomic profiles of pediatric AML risk are sex-specific. In females, four predictors of AML were putatively annotated as ceramides, a class of metabolites that has been linked with cancer cell proliferation. In females, two metabolite predictors of AML were strongly correlated with breastfeeding duration, indicating a possible biological link between this putative protective risk factor and childhood leukemia. In males, a heterogeneous metabolite profile of AML predictors was observed. Replication with larger participant numbers is required to validate findings.

Keywords: Breastfeeding; Cancer; Dried blood spot; Etiology; Exposome; Sex disparity.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Computational Biology / methods
Dried Blood Spot Testing* / methods
Female
Humans
Infant, Newborn
Leukemia, Myeloid, Acute / diagnosis*
Leukemia, Myeloid, Acute / etiology
Leukemia, Myeloid, Acute / metabolism*
Male
Metabolome
Metabolomics* / methods
Prognosis
Sex Factors

Abstract

Publication types

MeSH terms

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