Bone-Marrow Adipocytes Integrate Dietary Lipids to Reprogram Leukemia Metabolism and Therapy Response

Dr. Rahbani is focused on why obese patients have poorer outcomes and higher relapse rates in acute lymphoblastic leukemia (ALL). He posits that dietary lipid composition and the type of fat cells in a patient’s bone marrow can influence chemotherapy resistance. To pursue this hypothesis, Dr. Rahbani has established an innovative co-culture system that successfully grows leukemia cells alongside freshly isolated bone marrow fat cells, so that he can directly observe how fat cells might be implicated in supporting ALL. He will also use mice on controlled diets to observe how diet affects leukemia progression.

Dr. Rahbani’s Young Investigator Award will focus on two distinct questions: First, not all dietary lipids are built the same way; the effect of individual fatty acids plays a major role. He points out that saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) can exert both opposing and complementary effects on tumor growth depending on cellular context, metabolic state and nutrient availability. Dr. Rahbani hopes to understand how the mix of dietary lipids may reprogram bone marrow fat cells to alter ALL metabolism and chemotherapy sensitivity. Second, he’d like to find out if a calorie restricted diet can have an effect on therapy resistance through the bone marrow fat cell system by causing bone marrow adipocytes to modulate the SFA/MUFA balance. Dr. Rahbani hopes that we may be able to strengthen chemotherapy through dietary intervention or by developing treatments to block fat-leukemia interactions, both would likely be treatments with low toxicity that are easy to combine with the current status of care, offering a low cost/high leverage way to improve ALL patient outcomes.