Tumor-suppressive role for Notch signaling in acute myeloid leukemia
Project/Area Number |
25860778
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Hematology
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Research Institution | University of Tsukuba |
Principal Investigator |
TAKAYASU Kato 筑波大学, 医学医療系, 助教 (20646591)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 急性骨髄性白血病 / Notchシグナル / FLT3 / Hes1 |
Outline of Final Research Achievements |
In leukemogenesis, Notch signaling can be up and downregulated in a context-dependent manner. The transcription factor hairy and enhancer of split-1 (Hes1) is well-characterized as a downstream target of Notch signaling, and represses target gene expression. We report that deletion of the Hes1 gene in mice promotes acute myeloid leukemia (AML) development. We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. We also found that the expression level of FLT3 mRNA was negatively correlated with those of HES1 in patient AML samples. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development, probably by downregulating FLT3 expression.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Hes1 suppresses acute myeloid leukemia development through FLT3 repression2014
Author(s)
Kato T, Sakata-Yanagimoto M, Nishikii H, Miyake Y, Yokayama Y, Asabe Y, Kamada Y, Ueno M, Obara N, Suzukawa K, Hasegawa Y, Kitabayashi I, Uchida K, Hirao A, Yagita H, Kageyama R, Chiba S
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Journal Title
Leukemia
Volume: 29
Issue: 3
Pages: 576-585
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Therapeutic model by Notch2 agonist in acute myeloid leukemia.2014
Author(s)
Takayasu Kato, Mamiko Sakata-Yanagimoto, Yasuyuki Miyake, Hidekazu Nishikii, Yasuhisa Yokoyama,Naoshi Obara, Kazumi Suzukawa, Issay Kitabayashi, Hideo Yagita, Ryoichiro Kageyama, Shigeru Chiba.
Organizer
第76回日本血液学会
Place of Presentation
大阪
Year and Date
2014-10-31 – 2014-11-02
Related Report
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[Presentation] Hes1 Suppresses Acute Myeloid Leukemia Development in Conjunction with FLT3 Repression.2014
Author(s)
Takayasu Kato, Mamiko Sakata-Yanagimoto, Yasuyuki Miyake, Hidekazu Nishikii, Yasuhisa Yokoyama,Naoshi Obara, Kazumi Suzukawa, Issay Kitabayashi, Hideo Yagita, Ryoichiro Kageyama, Shigeru Chiba.
Organizer
第5回JSH国際シンポジウム
Place of Presentation
浜松
Year and Date
2014-05-24 – 2014-05-25
Related Report
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