Molecular reactivity in maternal pregnancy blood and neonatal dried blood spots is associated with risk of pediatric acute lymphoblastic leukemia

Abstract Background: Most pediatric leukemia forms early in life, but early life biology and biomarkers for screening remain undefined. We will perform direct molecular measurements in neonatal dried blood spots (DBS) and maternal pregnancy serum to identify early life biological signatures of pediatric acute lymphoblastic leukemia (ALL). Methods: In a nested case-control study design, we obtained mother-infant paired samples from second trimester pregnancy serum and neonatal DBS from 122 children diagnosed with pediatric ALL and 122 matched cancer-free controls. Using liquid chromatography–high resolution mass spectrometry, we performed untargeted metabolomics. The data-driven Reactomics approach was used to identify quantitative paired mass differences (qPMDs) that represent molecular changes in the samples. We identified qPMDs associated with ALL risk, and assessed linolenic and linoleic acid as potential ALL biomarkers. Results: Overall, the nine selected qPMDs in DBS were more strongly associated with ALL than the 16 qPMDs in maternal serum. Several of the selected qPMDs were highly correlated suggesting that these qPMDs may represent biological reactivity hubs of metabolic pathways important in leukemogenesis. We also observed a suggestive positive but not significant association between linolenic and linoleic acid in the DBS of children diagnosed with ALL at ages 5 years or older (N=13) and matched controls (N=13). Conclusions: While biological interpretation of Reactomics analysis for clinical intervention is currently limited, our study supports the presence of molecular reaction changes in early life associated with later pediatric ALL. Impact: Reactomics analysis revealed potential biomarkers in neonatal samples linked with later diagnosis of ALL.