Description:The obesity pandemic currently affects over 70 million Americans and over 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (e.g., SARS-CoV-2 et al.), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. It has been demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multi-drug chemoresistance. Furthermore, it has been demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used an untargeted metabolomics mass spectroscopy approach to define adipocyte-induced changes in B-cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells which are associated with metabolism. In all, our data increases our understanding of pathways which may promote chemoresistance in human B-ALL.