2014 Fiscal Year Final Research Report
Leukemogenesis between NUP98-HOX fusion genes and concomitant mutations
| Project/Area Number |
24591550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | NUP98 / HOX / FLT3 / RAS / WT1 |
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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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| Free Research Field |
血液学、腫瘍学、再生医療学
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