Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells

Abstract

SummaryAcute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, it is unclear whether AML cells could establish beneficial metabolic interactions with stromal cells. Here, we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption. By performing transcriptome analysis and tracer-based NMR studies, we show that stromal cells present a higher rate of glycolysis, and that the secreted acetate derives from pyruvate via a reactive oxygen species (ROS)-mediated process. Our data also reveals that AML cells transfer ROS to stromal cells using gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells that could be exploited as adjuvant therapy.