Abstract 3269: Rebalancing systemic and cellular energy dysmetabolism in Chronic Lymphocytic Leukemia through exercise training

Abstract Introduction: Chronic lymphocytic leukaemia (CLL) cells abnormally express lipoprotein lipase (LPL), an enzyme typically restricted to adipocytes and myocytes for lipid-mediated energy utilisation. This enables CLL cells to store and utilise lipids, potentially competing with or diverting resources from healthy tissues. In vitro studies suggest that reducing fatty acid availability may limit CLL proliferation; however, little is known about how patients can modulate this process in vivo. Exercise training offers a systemic, non-pharmacological approach to counter metabolic dysregulation, with potential benefits for tumour control and overall health. Methods: We conducted a 12-week exercise trial involving five treatment-naive (TN-CLL) and five previously treated (Td-CLL) patients. We assessed the metabolic fate of ingested lipids before (Baseline) and after (Post-Intervention) the program. Patients consumed a meal containing 200mg palmitic acid tracer (13CPA), and blood samples were collected hourly for 3 hours (T0h-T3h). We assessed 13CPA enrichment in plasma triacylglycerol (TAG) and non-esterified fatty acids (NEFA), and total fatty acids in immune cells (PBMC) using mass spectrometry, and data were analysed using RM-ANOVA. Results: Post-meal ingestion, 13CPA enrichment in plasma TAG and NEFA increased steadily from T1h-T3h (p<0.001). At Baseline T3h, TN-CLL exhibited higher plasma 13CPA-TAG and unlabelled PA-TAG incorporation than Td-CLL (p<0.001). Post-Intervention T3h, TN-CLL 13CPA-TAG levels decreased (p<0.05) and were no longer significantly different than Td-CLL. TN-CLL 13CPA-NEFA enrichment increased post-Intervention compared to Td-CLL (p<0.05), suggesting enhanced 13CPA-TAG hydrolysis. Similarly, 13CPA uptake into PBMCs, which was higher in TN-CLL at Baseline T3h (p<0.05), reduced Post-intervention. Conclusion: This pilot study demonstrates the feasibility of stable isotope tracing to assess in vivo lipid uptake in CLL. Exercise training in TN-CLL patients reduced lipid uptake, suggesting a shift towards a more balanced and healthier metabolic profile. Further research is needed to determine whether exercise can disrupt the lipid dependence of CLL cells. Citation Format: Uzma Zaheer, Ellie Miles, Angela Avramovska, Vithushan Srikumaran, Andrew Hulton, Long Li, Caitlin Jeary, Andrea Sitlinger, Renata Walewska, Barbara Fielding, David Bartlett. Rebalancing systemic and cellular energy dysmetabolism in Chronic Lymphocytic Leukemia through exercise training [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3269.