1996 Fiscal Year Annual Research Report

乳児白血病における11q23転座に関連する遺伝子の単離とその解析

Research Project

Project/Area Number	08457220
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The University of Tokyo
Principal Investigator	林泰秀東京大学, 医学部附属病院, 講師 (30238133)
Co-Investigator(Kenkyū-buntansha)	森脇浩一東京大学, 医学部附属病院, 助手 (10251274) 小林美由紀東京大学, 医学部附属病院, 助手 (60205391) 柳澤正義東京大学, 医学部附属病院, 教授 (90049031) 別所文雄東京大学, 医学部附属病院, 助教授 (40010285)
Keywords	白血病 / 11q23転座 / MLL遺伝子 / 乳児白血病
Research Abstract	乳児白血病の約70%にMLL遺伝子の再構成がみられ、この遺伝子が発症と進展に重要な役割を有する。我々はこれまでt(5;6;11)-乳児白血病の切断点のクローニングより6q27に座位するAF6遺伝子と、5q12に座位するAF-5α遺伝子を単離した。今年度はこれらの遺伝子の性状を検討した。種々の組織での発現をみると、神経系と肝臓での発現がみられ、特にマウスの胎児の肝臓での発現が強くみられた。さらにマウスの32Dcl 3細胞に遺伝子導入により強制発現をさせ、種々の実験を行ったが、この遺伝子の導入によりアポトーシスが阻害される事が判明し、詳細な検討を継続している。さらに現在保有しているt(11;16)、t(11;22)、t(11;15)、t(5;11)、t(11;17)等の白血病細胞を用いてcDNAライブラリーを作り、MLL遺伝子の再構成を用いて相手遺伝子の単離を試みたところ、前3核型より相手遺伝子の単離に成功した。とれた遺伝子はいずれも癌抑制遺伝子の範疇の遺伝子であり、その内の2つは細胞の転写の際に必須な重要な遺伝子であった。種々の組織での発現等、その産物の性状の詳細な検討を通じて、造血組織の発生・分化における役割と白血病発症における役割を解明している。現在、それぞれのキメラcDNAを単離し、マウスの32Dcl 3細胞への強制発現をさせ、発現の前後での発現の違いをDifferential Display法で検討しつつある。また、transgenic mouseとknock out mouseの作成も考えて進めているところである。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Tomohiko Taki: "Fusion of the MLL gene with two different genes,AF6 and AF-5α,by a complex translocation involving chromosomes 5,6,8 and II in infant leukemia" Oncogene. 13. 2121-2130 (1996)
[Publications] Shigetoshi Kobayashi: "Mutations of the Btk gene in twelve unrelated families with X-linked agammaglobulinemia in Japan:Immunological phenotypes are inconsistent with the location of the mutations" Human Genetics. 97. 424-430 (1996)
[Publications] Hiroaki Ohnishi: "Infrequent mutations of the P53 gene in hepatoblastomas" Gene Chromosomes Cancer. 15. 187-190 (1996)
[Publications] Hiroaki Ohnishi: "Homozygous deletions of P16/MTS1 and P15/MTS2 genes in t(1;19)-negative but not in t(1;19)-positive β precursor acuto lymphoblastic leukemia in childhood" Leukemia. 10. 1104-1110 (1996)
[Publications] Tomohiko Taki: "Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia." Leukemia. 10. 1303-1307 (1996)
[Publications] Kakuda: "A novel human leukaemic cell line,CTS,has a t(6;11)chromosomal translocation and characteristics of pluripotent stem cells." British Journal of Haematology. 95. 306-318 (1996)
[Publications] Yoshiaki Tsuchida: "Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene:Amplified or not amolified?-Overriew." Tumor Biology. 17. 65-74 (1996)
[Publications] Akira Inoue: "Competitive polymerase chain reaction for the quantification of N-myc gene number in neuroblastoma." Tumor Biology. 17. 262-270 (1996)
[Publications] Atushi Ohshima: "11q23 aberation is an additional chromosomal change in de novd acute leukemia after treatment with Etoposido and Mitoxantrone." American Journal of Hematology. 53. 264-266 (1996)
[Publications] Junko Takita: "Deletion map of chromosome q and P16(CDKN2A)gene alterations in neuroblastoma." Cancer Research. 1997年4月(発表予定). (1997)
[Publications] Kohmei Ida: "Deletion of chimeric mRNA by reverse transcriptase chain reaction for diagnosis and monitering of acute leukemi as with 11q23 abnormalities" Medical Pediatric Oncology. (in press).
[Publications] Hirofumi Kobayashi: "Inversion of chromosome 11,Tnv(11)(P15q22)as a recurring chromosomal aberration associated with de nove and secondary myeloid malignancies." Gene Chromosomes Cancer. (in press).

1996 Fiscal Year Annual Research Report

乳児白血病における11q23転座に関連する遺伝子の単離とその解析

Principal Investigator

林 泰秀 東京大学, 医学部附属病院, 講師 (30238133)

Research Products

[Publications] Tomohiko Taki: "Fusion of the MLL gene with two different genes,AF6 and AF-5α,by a complex translocation involving chromosomes 5,6,8 and II in infant leukemia" Oncogene. 13. 2121-2130 (1996)

[Publications] Shigetoshi Kobayashi: "Mutations of the Btk gene in twelve unrelated families with X-linked agammaglobulinemia in Japan:Immunological phenotypes are inconsistent with the location of the mutations" Human Genetics. 97. 424-430 (1996)

[Publications] Hiroaki Ohnishi: "Infrequent mutations of the P53 gene in hepatoblastomas" Gene Chromosomes Cancer. 15. 187-190 (1996)

[Publications] Hiroaki Ohnishi: "Homozygous deletions of P16/MTS1 and P15/MTS2 genes in t(1;19)-negative but not in t(1;19)-positive β precursor acuto lymphoblastic leukemia in childhood" Leukemia. 10. 1104-1110 (1996)

[Publications] Tomohiko Taki: "Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia." Leukemia. 10. 1303-1307 (1996)

[Publications] Kakuda: "A novel human leukaemic cell line,CTS,has a t(6;11)chromosomal translocation and characteristics of pluripotent stem cells." British Journal of Haematology. 95. 306-318 (1996)

[Publications] Yoshiaki Tsuchida: "Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene:Amplified or not amolified?-Overriew." Tumor Biology. 17. 65-74 (1996)

[Publications] Akira Inoue: "Competitive polymerase chain reaction for the quantification of N-myc gene number in neuroblastoma." Tumor Biology. 17. 262-270 (1996)

[Publications] Atushi Ohshima: "11q23 aberation is an additional chromosomal change in de novd acute leukemia after treatment with Etoposido and Mitoxantrone." American Journal of Hematology. 53. 264-266 (1996)

[Publications] Junko Takita: "Deletion map of chromosome q and P16(CDKN2A)gene alterations in neuroblastoma." Cancer Research. 1997年4月(発表予定). (1997)

[Publications] Kohmei Ida: "Deletion of chimeric mRNA by reverse transcriptase chain reaction for diagnosis and monitering of acute leukemi as with 11q23 abnormalities" Medical Pediatric Oncology. (in press).

[Publications] Hirofumi Kobayashi: "Inversion of chromosome 11,Tnv(11)(P15q22)as a recurring chromosomal aberration associated with de nove and secondary myeloid malignancies." Gene Chromosomes Cancer. (in press).

林泰秀東京大学, 医学部附属病院, 講師 (30238133)