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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| Project Status |
Completed (Fiscal Year 2014)
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| 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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| Keywords | NUP98 / HOX / FLT3 / RAS / WT1 / NUP98-HOXA9 / NRAS / 白血病 / HOXA9 / FLT3-ITD |
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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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Report
(4 results)
Research Products
(12 results)
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[Presentation] Myeloid Cells having NUP98-HOX Fusion Genes with Simultaneous FLT3, NRAS, or WT1 Mutations Confer Growth Advantage, Inhibits Differeniation/Apoptosis, and Augment Self-Renewal.2014
Author(s)
Takeshi Taketani, Miho Hattori, Mariko Abe, Tomohiro Hirade, Seiji Fukuda, Seiji Yamaguchi.
Organizer
56rd American Society of Hematology Annual Meeting
Place of Presentation
The Moscone Center (San Francisco, USA）
Year and Date
2014-12-06 – 2014-12-09
Related Report
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