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Figure 3. Bone marrow adipocytes promote fatty acid metabolism in AML. (A) Fatty acids derived through lipolysis of stored triglycerides in adipocytes induce upregulation of PPARG, CD36, and FABP4 gene transcription, which stimulates fatty acid endocytosis. In mitochondria, fatty acids are metabolized through fatty acid oxidation (FAO), decreasing mitochondrial reactive oxygen species (ROS) formation and intracellular oxidative stress, thereby reducing apoptosis; (B) transcriptional regulation and fatty acid metabolism pathways maintain AML cells in a quiescent state. Activation of AMPK, upregulation of p38 and associated induction of autophagy, and upregulation of antiapoptotic HSP chaperone proteins in this state lead to chemoresistance; (C) in mitochondria, fatty acids are consumed for FAO, resulting in diminished formation of mitochondrial ROS and decreased intracellular oxidative stress. Inhibition of FAO induces an integrated stress response that stimulates transcriptional activation of ATF4 and promotes apoptosis induced by chemotherapy. ADIPOR1: Adiponectin receptor 1; ATF4: activating transcription factor 4; AMPK: AMP-activated protein kinase; FABP4: fatty acid binding protein 4; p38: p38 mitogen-activated protein kinase.