| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
To elucidate the pathogenesis of acute myeloid Leukemia with NUP98-HOX fusions, we examined the function of NUP98-HOXA9 fusion gene (NHA9) and the concomitant mutations, FLT3 internal tandem duplication (FLT3-ITD), NRAS G13V mutation (NRASMT), and WT1 R250W mutation (WT1MT). IL3-independent 32D cellular growth was significantly increased in the cells co-transfected with NHA9/FLT3-ITD, NHA9/RASMT and NHA9/WT1MT. Only cells transfected with NHA9/FLT3-ITD decreased differentiated markers, CD11b and Gr1. In all transfected cells, annexin V positive/propidium iodide negative apoptotic cells did not declined, and monodansylcadaverine used to reveal autophagic vacuoles after tamoxifen was not incorporated. Transfection of NHA9/FLT3-ITD and NHA9/NRASMT significantly increased the number of colony forming unit. These suggested that NHA9 with the simultaneous gene mutations obtained growth advantage because of augmentation of self-renewality, resulted in contribution to leukemogenesis.
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