Relapse stubbornly continues to limit survival for children with B-cell progenitor acute lymphoblastic leukemia (B-ALL). B-ALL cells accumulate at the developmental checkpoint regulating the transition from pro-B to pre-B cells and express the pre-B cell receptor (preBCR). B-ALL samples have previously been categorized as preBCR positive and preBCR negative subtypes. We previously found that pre-B cells with active preBCR signaling are present at diagnosis and highly predictive of relapse, termed relapse predictive cells (RPCs) (Good et al. Nature Med 2018). Whole transcriptome sequencing of pre-B RPCs from patient samples demonstrated enrichment of gene signature pathways is involved in oxidative phosphorylation (OXPHOS), pyrimidine metabolism, and glycolysis pathways compared to pre-B cells from patients in complete remission. Thus, we hypothesized that RPCs have unique metabolic demands driven by their active signaling.