2002 Fiscal Year Final Research Report Summary
Isolation and characterization of the partner genes of MLL in acute leukemia with 11q23 translocation
| Project/Area Number |
12470166
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKI Tomohiko The University of Tokyo, The University of Tokyo, Faculty of Medicine, Research Associate (50322053)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yasuhide The University of Tokyo, Faculty of Medicine, Lecturer (30238133)
IDA Kohmei The University of Tokyo, Faculty of Medicine, Research Associater (60313128)
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| Project Period (FY) |
2000 – 2002
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| Keywords | 11q23 translocation / MLL gene / Acute leukemia / SEPTIN6 gene / LCX gene / LAF4 gene / AF4 gene / AF5q31 gene |
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| Research Abstract |
We showed that the MLL gene on 11q23 was fused to the SEPTIN6 gene on Xq24, a human homologue to mouse Septin6, in three de novo infant acute myeloid leukemia (AML) with complex chromosomal abnormalities involving 11q23 and Xq22-24. SEPTIN6 consisted of at least 12 exons and was predicted to encode at least two types of proteins by alternative splicing. The SEPTIN6 protein is homologous to septin family members including CDCREL1 and AF17q25/MSF, which generate fusion products with MLL. The MLL-SEPTIN6 fusion proteins contain almost the entire septin protein, similar to MLL-CDCREL1 and MLL-AF17q25/MSF. We next showed that the MLL gene on 11q23 was fused to the LCX (leukemia-associated protein with a CXXC domain) gene on 1Oq22 in a de novo adult AML-M2 with trilineage dysplasia having t(10;11)(q22;q23). LCX consisted of at least 12 exons and was predicted to encode a 2136-amino-acid protein with an estimated molecular mass of 235.3 kDa. The LCX protein had a zinc-binding CXXC domain that MLL also contains within a methyltransferase domain, three nuclear localization signals, an alpha-helical coiled-coil region, and two homologous regions to CG2083 proteins of Drosophila melanogaster. The MLL-LCX fusion protein lacked a CXXC domain of LCX, but retained an alpha-helical coiled-coil region at the COOH terminus, similar to MLL-SEPTIN6, We also showed that the LAF4 gene on 2q11.2-12 was fused to the MLL gene on 11q23 in a pediatric patient with CD10 positive acute lymphoblastic leukemia (ALL) having t(2;11)(q11;q23). The LAF4 gene, which encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential, is thought to have a role in early lymphoid development. The LAF4 protein was homologous to AF4 and AF5q31 proteins that are fused to MLL in infant early pre-B ALL and the breakpoint of LAF4 was located within the region homologous to the transactivation domain of AN and AF5q31.
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[Journal Article] SEPTIN6, a human homolog to mouse Septin6, is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24.2002
Author(s)
Ono R, Taki T, Taketani T, Kawaguchi H, Taniwaki M, Okamura T, Kawa K, Kikuchi A, Hanada R, Kobayashi M, Hayashi Y.
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Journal Title
Cancer Res 62
Pages: 333-337
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Co-duplication of the MLL and FLT3 genes in patients with acute myeloid leukemia.2001
Author(s)
Jamal R, Taketani T, Taki T, Bessho F, Hongo T, Hamaguchi H, Horiike S, Taniwaki M, Hanada R, Nakamura H, Hayashi Y.
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Journal Title
Genes Chromosomes Cancer 31
Pages: 187-190
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] t(10 ; 11)-acute myeloid leukemias with MLL- AF10 and MLL-ABI1 chimeric transcripts : Specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines.2001
Author(s)
Shibuya N, Taki T, Mugishima H, Chin M, Tsuchida M, Sako M, Kawa K, Ishii E, Miura I, Yanagisawa M, Hayashi Y.
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Journal Title
Genes Chromosomes Cancer 32
Pages: 1-10
Description
「研究成果報告書概要(欧文)」より
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