2016 Fiscal Year Final Research Report
Leukemogenicity of the RCSD1-ABL1 gene
| Project/Area Number |
26461434
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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 |
Hematology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Inokuchi Koiti 日本医科大学, 大学院医学研究科, 大学院教授 (10203267)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | RCSD1 / ABL1 / ALL / Ba /F3 / TKI / Tyk2 |
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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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| Free Research Field |
血液内科
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