1997 Fiscal Year Final Research Report Summary
Analysis of tumor suppressor gene in childhood leukemia and its application to clinical aspects
| Project/Area Number |
08670857
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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 |
Pediatrics
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| Research Institution | University of Tokyo |
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Principal Investigator |
SIBUYA Kazuhiko Univ.of Tokyo, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 助手 (80206151)
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| Co-Investigator(Kenkyū-buntansha) |
ISODA Takayoshi Univ.of Tokyo, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 助手 (80272574)
KOBAYASHI Miyuki Univ.of Tokyo, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 助手 (60205391)
HAYASHI Yasuhide Univ.of Tokyo, Faculty of Medicine, Associate Professor, 医学部・附属病院, 講師 (30238133)
YANAGISAWA Masayoshi Univ.of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (90049031)
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| Project Period (FY) |
1996 – 1997
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| Keywords | acute lymphoblastic leulemia / p16 gene / p15 gene / p53 gene / RAS gene / tumor suppressor gene / methylation |
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| Research Abstract |
Homozygous deletions (HD) of p16 and p15 genes and mutations of p16, RAS and p53 genes ere examined in B precursor acute lymphoblastic leukemia (ALL). Of 10 cell lines without t(1 ; 19), HD was found in 8 (80%), and a rearrangement of p16 in one cell line (10%). In contrast, only one (20%) of the 5 cell lines with t(1 ; 19) showed HD or rearrangement of p16/p 15 gene. Thirteen of 60 (22%) primary samples demonstrated HD of the p16 gene. No case with t(l ; 19) showed HD of the p16 gene (0/13), while cases without t(1 ; 19) showed considerable incidence of HD of the p16 gene (13/47,28%). Nine of 45 (20%) samples at diagnosis and four of 22 (18%) samples at relapse showed HD of p16. The similarity of the rate in these two groups raises the question of the role of p16 gene in progression of B precursor ALL.Remarkably, mutations were found in 3 of the primary cases (5%). As for leukemia with MLL rearrangement (MLL+), HD of the p16 and p15 genes was found in 5 (11%) of 19 acute myeloid leuke
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mias (AMLs), Patients with HD of pl6 and p15 genes showed higher average leukocyte counts and lower survival rates than those with normal p16 and p15 genes (14.3 vs 30.7%, not significant). PCR-single strand conformation polymorphism (SSCP) showed no mutationin in the 32 patients tested. Our results suggest that alterations of 16 and p15 genes are involved in a subset of acute leukemias with MLL+ not only of lymphoid but also of myeloid phenotype. Mutations of the p53 gene were found in 3 of 57 (5%) T-ALL patients at diagnosis, I of 14 (7%) patients at relapse and in 12 of 18 (67%) cell lines. All patients with p53 mutations in the course of disease died. Mutations of the p21 gene were not identified in 71 fresh samples and in 18 cell lines. N-RAS mutations were found in 2 of 57 (4%) fresh T-ALL patients at diagnosis, and 4 of 18 cell lines (22%), whereas no mutations were detected in any samples at relapse. Alterations of the p16 gene were found in 18 of 47 (38%) patients at diagnosis and in 7 of 14 (50%) at relapse (not significant). There were no differences in the frequency of alteration of the p16 and p15 genes between event-free patients and the remaining patients. Furthermore, we found the methylation of p16 gene in 3 of 7 patients lacking homozygous deletions, suggesting higher frequency of p16 inactivation than previous reports in T-ALL. Less
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[Publications] Ohnishi H,Guo SX,Ida K,Taki T,Naritaka S,Bessho F,Yanagisawa M,Hanada R,Eguchi M,Kamada N,Kita K,Yamamori S,Hayashi Y.: "Alteration of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features." Leukemia. 11. 2120-2124 (1997)
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「研究成果報告書概要(欧文)」より
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