Intracellular Chiral Metabolome in Pediatric Leukemia

Aberrations in the immunoglobulin heavy chain (IGH) locus are associated with poor prognosis in pediatric precursor B-cell acute lymphoblastic leukemia (BCP-ALL) patients. The primary objective of this pilot study is to enhance our understanding of the IGH phenotype by exploring the intracellular chiral metabolome. Leukemia cells were isolated from the bone marrow of BCP-ALL pediatric patients at diagnosis and at the end of induction therapy (EIT). The samples’ metabolome and transcriptome were characterized using untargeted chiral metabolomic and next-generation sequencing transcriptomic analyses. For the first time D- amino acids were identified in the leukemic cells' intracellular metabolome from the bone marrow niche. Chiral metabolic signatures at both diagnosis and EIT were indicative of a resistant phenotype. Through integrated network analysis and Pearson correlation, confirmation was obtained regarding the association of the IGH phenotype with several genes linked to poor prognosis. The findings of this study have contributed to the understanding that the chiral metabolome plays a role in the poor prognosis observed in an exceptionally rare patient cohort. The findings include elevated D-amino acid incorporation in the IGH group, the emergence of several unknown, potentially enantiomeric, metabolites, and insights into metabolic pathways that all warrant further exploration.