2004 Fiscal Year Final Research Report Summary
Active mutation of c-kit gene in acute myeloid leukemia
| Project/Area Number |
15591002
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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 | Mie University |
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Principal Investigator |
NISHII Kazuhiro Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (50332713)
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| Project Period (FY) |
2003 – 2004
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| Keywords | c-kit / mutation / acute myeloid leukemia / t(8;21) / prognostic factor / tyrosine kinase / abnormal chromosome |
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| Research Abstract |
The (8;21) translocation is one of the most common chromosomal abnormality in AML and is associated with good clinical outcome. However, the clinical features of t(8;21)AML with additional genetic aberrations such as mutation have not been well elucidated. In this study, we examined for the KIT mutation in 77 adult patients with de novo AML (M2 subtype) : 43 cases with t(8;21) and 34 cases without t(8;21). The juxtamembrane domain of KIT did not exhibit mutation, while mutation in the intracellular tyrosine kinase domain was detected at Asp816 in 7 of 77 cases and all these seven cases had t(8;21)(16.3% in t(8;21)AML). Western blotting revealed stem cell factor(SCF)-independent KIT activation in AML cells with mutations. Among t(8;21)AML, patients with mutations were significantly associated with leukocytosis (P=0.002) and poor overall survival (P<0.0001;5 year survival, 0% vs 73%). These cells with mutations highly expressed CD18 (P=0.01) and CD56 (P=0.005). When the Asp816 mutation was transfected into a SCF-dependent cell line, Mo7e, the cells grew rapidly and exhibited SCF-independent proliferation. These results indicate that Asp816 mutations of KIT are potentially suitable prognostic genetic markers for the t(8;21)AML patients and t(8;21)AML with mutations in KIT may be a distinctive subtype of t(8;21)AML.
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Research Products
(19 results)
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[Journal Article] Activities of granulocyte-macrophage colony-stimulating factor and interleukein-3 on monocytes2004
Author(s)
Suzuki H, Katayama N, Ikuta Y, Mukai K, Fujita A, Mitani H, Araki H, Miyashita H, Hoshino N, Nishikawa H, Nishii K, et al.
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Journal Title
Am J Hematol 75
Pages: 179-189
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia for the M0 subtype.2003
Author(s)
Matsuno N, Osato M, Yamashita N, Yanagida M, Nanri T, Fukushima T, Motoji T, Kusumoto S, Towatari M, Suzuki R, Naoe T, Nishii K, et al.
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Journal Title
Leukemia 17
Pages: 2492-2499
Description
「研究成果報告書概要(欧文)」より
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