| Project/Area Number |
26860820
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pediatrics
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2014-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| Keywords | T-ALL / ETP-ALL / MEF2C / BCL2 / ABT737 / ステロイド抵抗性 / ABT-737 / BCL2阻害剤 |
|---|
| 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.
|
