Runx1 as a Novel Therapeutic Target against Refractory Pediatric AML
| Project/Area Number |
15K19616
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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 | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | AML / Runx1 / FLT3/ITD / 急性骨髄性白血病 / 薬剤抵抗性 / 薬剤抵抗性白血病 / RUNX1 |
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| Outline of Final Research Achievements |
FLT3/ITD in patients with acute myeloid leukemia (AML), becomes refractory to FLT3 inhibitors. We investigated the function of RUNX1 in FLT3/ITD signaling. FLT3/ITD induced growth-factor-independent proliferation and impaired myeloid differentiation in 32D hematopoietic cells, coincident with increase of RUNX1 mRNA. Silencing RUNX1 expression significantly decreased proliferation and partially abrogated the impaired myeloid differentiation of FLT3/ITD+ 32D cells. Although the number of FLT3/ITD+ 32D cells declined in the presence of FLT3 inhibitor AC220, the cells became refractory to AC220, concomitant with increased expression of RUNX1. Silencing RUNX1 abrogated the emergence and proliferation of AC220-resistant FLT3/ITD+ 32D cells. Our data indicate that FLT3/ITD deregulates cell proliferation and differentiation and confers resistance to AC220 by up-regulating RUNX1 expression, suggesting that RUNX1 represents a therapeutic target in patients with refractory FLT3/ITD+ AML.
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Report
(4 results)
Research Products
(7 results)
