| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Leukemia cells can survive and proliferate under the metabolic stress environment of bone marrow. We aim to identify a specific metabolic inhibitor and clarify change of energy metabolism in refractory leukemia. 1) Based on anti-proliferative and energy metabolism inhibitory effects in human AML cells, AMPK inhibitor (Compound C) had a high anti-leukemic effect in MLL-rearranged (MLL-r) leukemia. 2) We analyzed metabolic change during the leukemia development process in the EVI1 high expression (EVI1+) MLL-r AML mice model by Extracellular flux analyzer, and revealed the predominant accelerated oxidative phosphorylation (OXPHOS) prior to activation of glycolysis and higher dependency on glutamine as energy source. We revealed that L-Asparaginase suppressed OXPHOS and cell proliferation of the EVI1+ AML cells effectively in vitro and in vivo. Further clarification of metabolic reprograming in leukemia cells can be a new tool to realize a breakthrough of refractory leukemia treatment.
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