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Tumor associated gene in chromosomal translocation in acute leukemia

Research Project

Project/Area Number 04454568
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionUniversity of Tokyo

Principal Investigator

HAYASHI Yasuhide  Univ.of Tokyo (Hospital), Pediatrics, Associate Professor, 医学部(病), 講師 (30238133)

Co-Investigator(Kenkyū-buntansha) HIRAI Hisamaru  Univ.of Tokyo (Hospital), Internal Medicine, Associate Professor, 医学部(病), 講師 (90181130)
KOBAYASHI Miyuki  Univ.of Tokyo (Hospital), Pediatrics, Assistant Professor, 医学部(病), 助手 (60205391)
KAMOSHITA Shigehiko  Univ.of Tokyo (Hospital), Pediatrics, Professor, 医学部(病), 教授 (60048973)
BESSHO Fumio  Univ.of Tokyo (Hospital), Pediatrics, Associate Professor, 医学部(病), 助教授 (40010285)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsacute leukemia / lymphoma / suppressor gene / translocation / E2A-PBX1 / TAL1 gene / MLL gene / TLS / FUS-ERG / 染色体転座 / 11q23転座 / 癌遺伝子 / 切断点近傍遺伝子 / AF6遺伝子 / 乳児白血病 / 遺伝子再構成 / 切断点遺伝子 / 染色体異常 / E2A遺伝子 / 分子生物学
Research Abstract

E2A-PBX1 chimeric mRNA,which was reported in t (1 ; 19)-acute lymphoblastic leukemia (ALL), was found in 10 of 40 ALL patients. p53 alteration was found in 2 of 20t (1 ; 19)-ALL at diagnosis, 4 of 4 at relapse and 4 of 5 cell lines. We conclude that p53 alteration is associated with relapse or progression. We examined TAL1 alteration in 99 hematological maligmacines and found the alteration in 10 T-ALL patients. Theses patients had similar immunophonotype, normal karyotype, good prognosis, resulting in a subset of T-ALL.TLS/FUS-ERG chimeric mRNA was found in all the 19t (16 ; 21)-acute myeloid leukemia (AML), 18 of whom died. We concluded that t (16 ; 21)-AML patient has a poor prognosis and should be treated by stem cell transplantation in the first remission. MLL gene analysis was preformed on leukemia with 11q23 abnormalities. We found that infant with MLL rearrangements was a poor prognosis. We also found 3 partner genes of MLL gene, AF-5alpha, CBP and p300 gene. We examined the role of these genes in the development of leukemia.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Kikuchi A,et al.: "Clinical significance of TAL1 gene alteration in child hood T-cell acute lymphoblastic leukemia and lymphome" Leukemia. 7. 946-953 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimizu K,et al.: "An ets-related gene,ERG,is rearranged in human myeloid leukemia with t(16;21) chromosomal thranslocation" Proc Natl Acad Sci USA. 90. 10280-10284 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichikawa H,et al.: "An RNA-binding protein TLS/FUS is fused to FRG in human myeloid leukemia with t(16;21) chromosomal translocation" Cancer Res. 54. 2865-2868 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kawamura M,et al.: "Mutation of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia." Blood. 85. 2546-2552 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohnishi H,et al.: "Homozygous deletion of p16/MTS1 gene are frequent but mutations are infrequent in childhood T-cell acute lymphoblastic" Blood. 86. 1269-1275 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taki T,et al.: "The t(11;16) (q23;p13) translocation in Myelodysplastic Syndrome Fuses the MLL gene to the CBP gene" Blood. 89. 3945-3950 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kikuchi A,Hayashi Y,Kobayashi S,Hanada R,Yamamoto K,Fujimoto J,Kaneko Y,Yamamori S.: "Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma." Leukemia. 7. 946-953 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimizu K,Ichikawa H,Tojo A,Kaneko Y,Maseki M,Hayashi Y,Ohira M,Asano S,Ohki M: "An ets-related gene, ERG,is rearranged in human myeloid leukemia with t (16 ; 21) chromosomal translocation." Proc Natl Acad Sci USA. 90. 10280-10284 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichikawa H,Shimizu K,Hayashi Y,Ohki M.: "An RNA-binding protein TLS/FUS is fused to FRG in human myeloid leukemia with t (16 ; 21) chromosomal translocation." Cancer Res. 54. 2865-2868 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kawamura M,Hayashi Y,Kobayashi S,Kikuchi A et al.: "Mutations of the p53 and ras genes in childhood t (1 ; 19)-acute lymphoblastic leukemia." Blood. 85. 2546-2552 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohnishi H,Kawamura M,Ida K,Hanada R,Hayashi Y,et al.: "Homozygous deletion of p16/MTS1 gene are frequent but mutations are infrequent in childhood T-cell acute lymphoblastic leukemia." Blood. 86. 1269-1275 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tomohiko Taki, Masahiro Sako, Masahiro Tsuchida, and Yasuhide Hayashi: "The t (11 ; 16) (q23 ; p13) Translocation in Myelodysplastic Syndrome Fuses the MLL Gene to the CBP Gene" Blood. Vol 89, No 11 (June 1). 3945-3950 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato,S: "Effects of herbimycin A and its devivgtiues on growth and defferenhation of philadelphia chromosome-position aotlg lywphig leuhewia cell lines" Leukemia Res. 18. 221-228 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mori,T: "Geym-line and somatic mutatiing of the APC gene in patients with Trucot syndorome and analysis of APC mutations in brain tunus" Genes Chromsomes Cancer. 9. 168-172 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichikawa,H: "An RNA-binding protein TLS/FUS is fused to FRG in human myeloid leuhemia with t(16;21) chromosonal translocation" Cancer Res. 54. 2865-2868 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujii,Y: "Chromosome analysis of the brain tumors in childhood" Gene Chromosomes Caucer. 9. 205-215 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitani,K: "Molecular analysis of the t(1;19)(q23;p13) translocation observed in adult leukemias" Jut J Hematol. 60. 267-271 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kawamura,M: "Mutatrins of the P53 and ras genes in childhood t(1;19)-acute lyuplichblastic leuheuid" Blood. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamamoto,K.: "J Clin Oncol" Effect of nuss screening on the incidencl of neuroblesteua in Saitama Prefectul(in press),

    • Related Report
      1994 Annual Research Report
  • [Publications] Ito,E: "Brit J Henuatol" Expression of erythroid-specitic genes in acuto megakayohlustic leuheuia and trausieut myeloproliferatiuo disirdes in Pown's syndrome(in press),

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyashita,T: "Molecular diversion of dominant subclones in vivo and in vitro in Ph-positive ALL." Leukemia. 7. 586-592 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kikuchi,A: "Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma." Leukemia. 7. 946-953 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sotomatsu,M: "Establishment of a new human pre-B acute lymphoblastic leukemia cell line(KMO-90)with 1;19 translocation carrying p53 gene alterations." Leukemia. 7. 1615-1620 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimizu,K.: "An ets-related gene,ERG,is rearranged in human myeloid leukemia with t(16;21)chromosomal translocation." Proc.Natl Acad Sci USA. 90. 10280-10284 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Komuro,H.: "Mutations of the p53 gene are involved in Ewing s sarcomas but not in neuroblastomas." Cancer Res. 53. 5284-5288 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,S.: "Effects of herbimycin A and its derivatives on growth and differentiation of Philadelphia chromosome-positive acute lymphoid leukemia cell lines." Leukemia Res. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Privitera,E.: "Different molecular consequences of 1;19 chromosomal translocation in childhood B cell precussor acute lymphoblastic leukemia" Blood. 79. 1781-1788 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayashi,Y.: "Leukoencephalopathy in children with t(1;19) acuto lymphoblastic leukemia" Lancet. 2. 316 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mitani K.: "Two myelodysplastic syndrome cases with the inv(11)(p15q23) as a sole chromosomal abnormality" Brit J.Haematol. 81. 512-515 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kikuchi A.: "Clinical significance of TAL1 gane alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma" Leukemia.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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