| Project/Area Number |
25860899
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Research Collaborator |
TOMITA Osamu 順天堂大学, 医学部, 助教
SUZUKI Ryo 東京理科大学大学院, 総合化学研究科
OCHI Kentaro 東京理科大学, 工学部
KOMARU Kanae 東京理科大学, 工学部
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 白血病 / シグナル伝達 / チロシンキナーゼ阻害剤 / B前駆細胞性急性リンパ芽球性白血病 / キメラ遺伝子 |
|---|
| Outline of Final Research Achievements |
Therapeutic application of tyrosine kinase inhibitors (TKIs) has significantly improved the outcome of BCR-ABL1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Recently, novel ABL1-related chimeric transcripts were identified. In this study, we investigated the functional characteristics of SNX2-ABL1 protein. IL-3-independent proliferative ability was acquired by induction of SNX2-ABL1 as similar as BCR-ABL1 in IL3-dependent mouse pro-B Ba/F3 cells. SNX2-ABL1-expressing Ba/F3 cells showed rather lower sensitivity against TKIs, especially dasatinib. Then, the mechanism of resistance to dasatinib was investigated. As a result, SNX2-ABL1-expressing Ba/F3 cells showed different phosphorylation pattern of those of BCR-ABL1 and the phosphorylation of intracellular proteins, especially CrkL, p44/42 MAPK, STAT5, are only partially inhibited by TKI treatment. From gene expression analysis, high expression of Igf-1 in SNX2-ABL1 expressing cells was observed.
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