2015 Fiscal Year Final Research Report
Development of new therapeutic strategy for ETP-ALL
Project/Area Number |
26860820
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Yoshida Hideki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10643546)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Keywords | T-ALL / ETP-ALL / MEF2C / BCL2 / ABT737 / ステロイド抵抗性 |
Outline of Final Research Achievements |
Early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL) has been identified as a high-risk subtype of pediatric T-ALL. Analysis of the gene expression patterns revealed that MEF2C was expressed at higher levels in ETP-ALL. Using human T-ALL and BaF3 cell lines with high expression levels of MEF2C, the present study tested whether the BCL2 inhibitor (ABT-737) restores the sensitivity to prednisolone (PSL), because MEF2C causes PSL resistance, possibly by augmenting the anti-apoptotic activity of BCL2. Treatment with PSL and ABT-737 caused a significant reduction in the IC50 of PSL in the MEF2C-expressing LOUCY cells, in addition to the MEF2C-transduced BaF3 cells. The combination treatment significantly accelerated the killing of primary leukemic blast cells of ETP-ALL with high expression levels of MEF2C, which were co-cultured with MS5 cells. These findings suggest that BCL2 inhibitors may be a therapeutic candidate for patients with ETP-ALL with high expression levels of MEF2C.
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Free Research Field |
医歯薬学
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