Tumor associated gene in chromosomal translocation in acute leukemia

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 04454568
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: University 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
• Keywords: acute leukemia / lymphoma / suppressor gene / translocation / E2A-PBX1 / TAL1 gene / MLL gene / TLS / FUS-ERG

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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