Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Outline of Final Research Achievements |
Two RCSD1-ABL1 cDNA were cloned from a cells of RCSD1-ABL1-positive acute leukemia.One is cDNA consisted of exon 3 of RCSD1/ exon 4 of ABL1 (R3A4), another is consisted of exon 2 of RCSD1/ exon 4 of ABL1 (R2A4). R3A4 and R2A4 were expressed in Ba/F3 cells using retrovectors. Using phosphorylation antibody array detected the increased phosphorylation of Tyk2 in R3A4-Ba/F3 cells. Wester blotting analysis confirmed the increased phosphorylation of Tyk2, although no increased phosphorylation of Tyk2 in R2A4-Ba/F3 cells. Tyrosine kinase inhibitor assays also showed the sensitivity of R3A4-Ba/F3 cells to the TKIS imatinib, dasatinib, and JAK2 inhibitor I, which is a pan family including Tyk2 inhibitor. R3A4-Ba/F3 cells showed sensitivity only to JAK-inhibitor I. These findings suggest that the kinase-activating pathways and sensitivities to TKIs vary between fusion sites of RCSD1-ABL1 in leukemogenesis.
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