Abstract 271: The effects of B-cell acute lymphoblastic leukemia cells on the adipose tissue microenvironment

Abstract

Abstract Obesity increases the risk of developing many cancers, including breast, colon, kidney, and acute lymphoblastic leukemia (ALL). We have previously shown that ALL cells are recruited to migrate into adipose tissue, where they are protected from chemotherapy. In vitro, ALL cells induce significant changes in adipocytes which may contribute to these protective effects. However, how ALL cells affect the complex cell populations found in adipose tissue in vivo remains unknown. We therefore conducted single-cell RNA sequencing (scRNAseq) of the non-adipocyte stromal vascular fraction (SVF) from adipose tissue in obese mice with and without implanted syngeneic BCR-ABL positive ALL. Differential expression analysis was performed on individual SVF cell types to compare ALL vs. control adipose tissue and pathway enrichment analysis was used in identifying altered molecular processes between conditions. SVF from leukemic mice showed substantial differences in gene expression compared to control mice, suggesting that the ALL potentially induces changes in the microenvironment. Some of the largest differences were found in adipose tissue macrophages, and pathway enrichment analysis identified neutrophil recruitment and regulation as one of the top ten pathways upregulated in adipose macrophages from leukemic mice (4.10 fold enrichment, p<1 × 10-17 by Fisher’s exact test). Selected macrophage genes of interest in this pathway included CYBB (Cytochrome B-245 Beta), a neutrophil interaction gene that has been associated with macrophage infiltration in gastric cancer, was expressed 2.28 log2-fold higher in macrophages from leukemic compared to nonleukemic mice (p<1 × 10−99 by Wilcoxon test). ITGAL (Integrin subunit alpha L), which has been shown to be involved in neutrophil recruitment and implicated in cancer cell growth and transformation was expressed 2.85 log2-fold higher in macrophages from leukemic mice (p<1 × 10−99). Interestingly, adipose from leukemic mice showed a population of neutrophils (1.9% of SVF cells), while neutrophils were largely absent in adipose from nonleukemic mice (<0.1% of SVF cells), which is consistent with macrophage involvement in neutrophil recruitment. Our findings highlight the importance of adipose tissue in the leukemia microenvironment and show that ALL cells can influence this microenvironment in complex ways. Further work will confirm and investigate these cell-cell interactions, potentially improving our understanding of how adipose tissue contributes to cancer mortality. Citation Format: Jia Tan, Michael Cohen, Jessica Ding, In Sook Ahn, Xia Yang, Steven D. Mittelman. The effects of B-cell acute lymphoblastic leukemia cells on the adipose tissue microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 271.