our results suggest that leukemia cells are vulnerable to oxidize efas via mitochondrial pathways. both EX and ranolazine reduced QLPs in approximately 50-degree of AML samples, which implies that FAO may support the maintenance of those leukemia initiating cells. The therapeutic importance of those in vitro effects is not evident in our in vivo leukemia type, where EX alone had no significant effect on leukemia burden or survival. Moreover, the system where pan Chk inhibitor EX and Ara C presented a therapeutic effect in vivo without demonstrating synergy in vitro continues to be unresolved. Nonetheless, our findings that genetic or pharmacological inhibition of FAO sensitized leukemia cells to ABT 737 and Nutlin 3a, and that EX offered a therapeutic advantage in a murine model of human leukemia in combination with ABT 737 or Ara C, generate proof principle that FAO could be a bona fide target for sensitizing hematological malignancies to agents that stimulate the intrinsic apoptotic pathway. In conclusion, our results lead to 2 practices. The first is that leukemia cells oxidize fatty acids. Uncoupling of oxidative phosphorylation promotes a shift of ATP generation from FAO to Papillary thyroid cancer glycolysis. 2nd, our data support the notion this metabolic adaptation in leukemias is fundamentally from the Bcl 2 apoptotic rheostat and might be targeted for therapeutic intervention. Although the precise mechanism through which FAO inhibitors supply a therapeutic advantage in conjunction with ABT 737 or Ara C in murine models of leukemia remain to be elucidated, we propose that modulation of fatty-acid metabolism might represent a novel strategy for the treatment of hematological malignancies. Practices Primary leukemia products. Bone marrow or peripheral blood samples were received for in vitro studies from patients with AML or CML. Samples were collected all through routine diagnostic procedures after informed consent was obtained, methods for studies in humans were approved by the Human Subjects Committee of the University of Texas M. D. Anderson Cancer Center. Mononuclear Dasatinib solubility cells were separated by Ficoll Hypaque density gradient centrifugation. Murine leukemia model. All studies in mice were reviewed and approved by the University of Texas M. D. Anderson Cancer Center IACUC. Via tail vein injection, we adopted 5 week old 01B74 athymic nude mice with 2 106 MOLM13 cells stably expressing a double Renilla luciferase GFP reporter. At two weeks after xenotransplantation, mice were randomized into 4 treatment sets of 9 mice per group and treated as follows: liposomal ABT 737, EX, ABT 737 plus EX, or empty liposomes as a control. In a different research, xenotransplanted mice were randomized into 4 treatment groups of 8 mice per group and treated. Leukemia stress was monitored by noninvasive imaging of isoflurane anesthetized mice injected i. p. with luciferin in the In vivo Imaging System, with complete imaging time of 1 minute.