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Furthermore, others have 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 a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell\u2013specific signature in patients associated with survival outcomes.<\/jats:p>","DOI":"10.1093\/jncimonographs\/lgad014","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T10:56:24Z","timestamp":1683197784000},"page":"12-29","source":"Crossref","is-referenced-by-count":10,"title":["The \u2018omics of obesity in B-cell acute lymphoblastic leukemia"],"prefix":"10.1093","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-6089","authenticated-orcid":false,"given":"Delaney K","family":"Geitgey","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA, USA"},{"name":"Aflac Cancer and Blood Disorders Center , Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA, USA"},{"name":"Aflac Cancer and Blood Disorders Center , Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten A","family":"Cottrill","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine , Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Jaffe","sequence":"additional","affiliation":[{"name":"Wallace H. 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