2006 Fiscal Year Final Research Report Summary
Crosstalk of FLT3 and integrin signal transduction pathway in acute myeloid leukemia
| Project/Area Number |
17590989
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
KATSUMI Akira Nagoya University, Graduate School of Medicine, Designated Assistant Proressor, 大学院医学系研究科, 特任講師 (80378025)
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| Co-Investigator(Kenkyū-buntansha) |
KAIBUCHI Kozo Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (00169377)
NAOE Tomoki Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (50217634)
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| Project Period (FY) |
2005 – 2006
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| Keywords | integrin / FLT3 / tyrosine kinase / PI3K / cell adhesion / extracellular matrix / leukemia |
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| Research Abstract |
We have investigated the effects of constitutive active FLT3 on activation of integrin by using 32D cells, MOLM-13, NAMO-2 cells.
1) Constitutive activation of FLT3 induced the adhesion of leukemia cell lines on extracellular matrix such as fibronectin.
2) Our group established the human leukemia cell line NAMO-2 that has FLT3/ITD mutation and can be maintained only on the mouse bone marrow stromal cell line (Abe A et al, Int J Hematol 2006). Addition of FLT3 inhibitor onto NAMO-2 induced the detachment of cell line from the HESS-5.
3) Our group established the α4β1 integrin activation assay by VCAM-1-Fc chimera protein. Incubation of 32D cells expressing FLT3/ITD with FLT3 inhibitor inactivated α4β1 integrin. Same results were observed in MOLM-13, which has FLT3/ITD mutation. Addition of FLT3 ligand to 32D-FLT3/ITD cells induced the activation of α4β1 integrin.
4) αvβ3 integrin activation is mediated by PI3K and is followed by increase in integrin binding to extracellular matrix proteins. The new integrin binding to extracellular matrix protein induce the activation of JNK/SAPK. These observations demonstrated the cross talk of integrin and other kinases signal transduction pathways.
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[Journal Article] Establishment of Stroma Dependent Human Acute Myelomonocytic Leukemia Cell Line, NAMO-2 with FLT3 Tandem Duplication.2006
Author(s)
Abe A, Kiyoi H, Ninomiya M, Yamazaki T, Murase T, Ozeki K, Suzuki M, Hayakawa F, Katsumi A. Emi N, Naoe T.
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Journal Title
Int J.Hematol. 84(4)
Pages: 328-36
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High Titer of ADAMTS13 Inhibitor Associated with Thrombotic Microangiopathy of the Gut and Skeletal Muscle after Allogeneic Hematopoietic Stem Cell Transplantation.2006
Author(s)
Adachi T, Matsushita T, Ichihashi R, Hirashima K, Ito M, Inukai A, Yokozawa T, Nishida T, Murata M, Hayashi M, Katsumi A. Kojima T, Saito H, Naoe T.
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Journal Title
Int J Hematol. 83(5)
Pages: 415-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fatal thrombosis of antithrombin-deficient mice is rescued differently in the heart and liver by intercrossing with low tissue factor mice. _2006
Author(s)
Hayashi M, Matsushita T, Mackman N, Ito M, Adachi T, Katsumi A, Yamamoto K, Takeshita K, Kojima T, Saito H, Murohara T, Naoe T.
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Journal Title
J Thromb Haemost. 4(1)
Pages: 177-85
Description
「研究成果報告書概要(欧文)」より
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