Identification of novel therapeutic targets against refractory AML using genome editing
Project/Area Number |
17K10111
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Shimane University |
Principal Investigator |
Fukuda Seiji 島根大学, 学術研究院医学・看護学系, 教授 (30273147)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 急性骨髄性白血病 / 薬剤耐性 / 薬剤抵抗 / FLT3/ITD / CXCL12 / 薬剤抵抗性 / ゲノム編集 / Flt3/ITD |
Outline of Final Research Achievements |
This study was to determine the molecular mechanism responsible for the refractory FLT3 mutated acute myeloid leukemia. Using the mRNA microarray screening, we identified a transcriptional factor Runx1 as a candidate molecule responsible for the resistance of the FLT3 mutated acute myeloid leukemia. Our subsequent analyses validate that Runx1 is indeed involved and modulate resistance regulated by chemokine Cxcl12 in FLT3 mutated acute myeloid leukemia cells. We identified that changes in expression level in FLT3 mutated acute myeloid leukemia cells, which was dependent on the magnitude of Cxcl12/Cxcr4 signaling, regulates resistance of FLT3 mutated acute myeloid leukemia against FLT3 inhibitors. This study suggest that Runx1 represents potential target for the treatment of FLT3 mutated acute myeloid leukemia that are refractory against FLT3 inhibitors.
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Academic Significance and Societal Importance of the Research Achievements |
急性骨髄性白血病の予後は芳しくない。特にFLT3変異陽性のケースは予後が悪い。近年、FLT3変異に対する抑制剤(FLT3抑制剤)が承認され使用されているが、大部分は治療抵抗性となる。治療抵抗性の分子メカニズムは様々なものが知られているが、この研究ではFLT3抑制剤の治療抵抗性のメカニズムを新たに見出した。すなわち、治療抵抗性を克服しうる新たな治療標的が同定できた。この研究をさらに発展させることでFLT3抑制剤の治療効果が改善し、患者の予後改善に結びつく可能性がある点で意義のある研究である。
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell2018
Author(s)
Hoggatt J, Singh P, Tate TA, Chou BK, Datari SR, Fukuda S, Liu L, Kharchenko PV, Schajnovitz A, Baryawno N, Mercier FE, Boyer J, Gardner J, Morrow DM, Scadden DT, Pelus LM
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Journal Title
Cell
Volume: 172
Pages: 191-204
Related Report
Peer Reviewed / Int'l Joint Research
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