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Analysis of the p53 gene mutations in acute myelogenous leukemia: The p53 gene mutations associated with a deletion of chromosome 17

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Abstract

In order to determine the relevance of the p53 tumor suppressor gene mutations in acute myelogenous leukemia (AML), we analyzed the p53 gene in genomic DNA of 18 unselected cases of AML by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. We detected three cases (16.7%) with the p53 gene mutations showing only the mutant alleles; the high incidence in cases with loss of a whole chromosome 17 (two of three) contrasted with the low incidence in cases without abnormalities of chromosome 17 (one of 15). These cases containing the mutations of the p53 gene showed a poor prognosis. Although we analyzed a rather small series of patients, these findings suggest that the p53 gene mutations might be involved in the progression and prognosis of at least some cases of AML.

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References

  1. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89:7491–7495

    PubMed  Google Scholar 

  2. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304–6311

    PubMed  Google Scholar 

  3. Lowe SW, Ruley HE, Jacks T, Houseman DE (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967

    PubMed  Google Scholar 

  4. Levine AJ, Momand J, Finlay CA (1991) The p53 tumor suppressor gene. Nature 351:453–456

    PubMed  Google Scholar 

  5. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumor types. Nature 342:705–708

    PubMed  Google Scholar 

  6. Ahuja H, Bar-Eli M, Advani SH, Benchimol S, Cline MJ (1989) Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. Proc Natl Acad Sci USA 86:6783–6787

    PubMed  Google Scholar 

  7. Feinstein E, Cimino G, Gale RP, Alimena G, Berthier R, Kishi K, Goldman J, Zaccaria A, Berrebi A, Canaani E (1991) p53 in chronic myelogenous leukemia in acute phase. Proc Natl Acad Sci USA 88:6293–6297

    PubMed  Google Scholar 

  8. Marshal R, Shtairid M, Talpatz M, Kantarjian H, Smith L, Beam M, Cork L, Trujillo J, Gutterman J, Deisseroth A (1990) Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. Blood 75:180–189

    PubMed  Google Scholar 

  9. Kurosawa M, Okabe M, Kunieda Y, Miyazaki T (1994) p53 Gene mutation in the chronic phase was not detected in the myeloid crisis of a chronic myelocytic leukemia case. Blood 83:2750–2752

    Google Scholar 

  10. Slingerland JM, Minden MD, Benchimol S, Cline MJ (1991) Mutation of the p53 gene in human acute myelogenous leukemia. Blood 77:1500–1507

    PubMed  Google Scholar 

  11. Fernaux P, Preudhomme C, Quiquandon I, Jonveaux P, Lai JL, Vanrumbeke M, Loucheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP (1992) Mutations of the p53 gene in acute myeloid leukemia. Br J Haematol 80:178–183

    PubMed  Google Scholar 

  12. Hu G, Zhang W, Deisseroth A (1992) p53 Gene mutations in acute myelogenous leukemia. Br J Haematol 81:489–494

    PubMed  Google Scholar 

  13. Gandini D, Cuneo A, Carli MG, Lanza F, Castoldi GL, del Senno L (1994) Total loss of p53 DNA sequences in acute myeloid leukemia. Leukemia Res 18:63–65

    Google Scholar 

  14. Jonveaux P, Fernaux P, Quiquandon I, Pignon JM, Lai JL, Loucheux-Lefebvre MH, Coossens M, Bauters F, Berger R (1991) Mutations in the p53 gene in myelodysplastic syndromes. Oncogene 6:2243–2247

    PubMed  Google Scholar 

  15. Ichikawa A, Hotta T, Takagi N, Tsushita K, Kinoshita T, Nagai H, Murakami Y, Hayashi K, Saito H (1992) Mutations of p53 gene and their relation to disease progression in B-cell lymphoma. Blood 79:2701–2707

    PubMed  Google Scholar 

  16. Sakashita A, Hattori T, Miller CW, Suzushima H, Asou N, Takatsuki K, Koeffler HP (1992) Mutations of the p53 gene in adult T-cell leukemia. Blood 79:477–480

    PubMed  Google Scholar 

  17. Neri A, Baldini L, Trecca D, Cro L, Polli E, Maiolo AT (1993) p53 Gene mutations in multiple myeloma are associated with advanced forms of malignancy. Blood 81:128–135

    PubMed  Google Scholar 

  18. Fernaux P, Jonveaux P, Quiquandon I, Lai JL, Pignon JM, Loucheux-Lefebvre MH, Bauters F, Berger R, Kerckaert JP (1991) p53 Gene mutations in acute myeloid leukemia with 17p monosomy. Blood 78:1652–1657

    PubMed  Google Scholar 

  19. Orita M, Suzuki Y, Sekiya T, Hayashi K (1989) Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5:874–879

    PubMed  Google Scholar 

  20. Gyllensten UB, Erlich HA (1988) Generation of single-strand DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85:7652–7656

    PubMed  Google Scholar 

  21. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Grahnick G, Sultan C (1985) Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 103:626–629

    PubMed  Google Scholar 

  22. Perucho M, Goldfarb M, Shimizu K, Lama C, Fogh J, Wigler M (1981) Human-tumor-derived cell lines contain common and different transforming genes. Cell 27:467–473

    PubMed  Google Scholar 

  23. Suzuki F, Sekiya T, Hayashi K (1991) Allele-specific polymerase chain reaction: a method for amplification and sequence determination of a single component among a mixture of sequence variants. Anal Biochem 192:82–84

    PubMed  Google Scholar 

  24. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    PubMed  Google Scholar 

  25. Nakai H, Misawa S, Toguchida J, Yandell DW, Ishizaki K (1992) Frequent p53 gene mutations in blast crisis of chronic myelogenous leukemia, especially in myeloid crisis harboring loss of a chromosome 17p. Cancer Res 52:6588–6593

    PubMed  Google Scholar 

  26. Fenaux P, Preudhomme C, Lai JL, Morel P, Beuscart R, Bauters F (1989) Cytogenetics and their prognostic value in de novo acute myeloid leukemia: a report on 283 cases. Br J Haematol 73:61–67

    PubMed  Google Scholar 

  27. Nakai H, Misawa S, Taniwaki M, Horiike S, Takashima T, Seriu T, Nakagawa H, Fujii H, Shimazaki C, Maruo N, Akaogi T, Uike N, Abe T, Kashima K (1994) Prognostic significance of loss of a 17p and p53 gene mutations in blast crisis of chronic myelogenous leukaemia. Br J Haematol 87:425–427

    PubMed  Google Scholar 

  28. Milner J, Medcalf EA (1991) Cotranslation of activated mutant p53 with wild-type drives the wild-type p53 protein into the mutant conformation. Cell 65:765–774

    PubMed  Google Scholar 

  29. Chin KV, Ueda K, Pastan I, Gottesman MM (1992) Modulation of activity of the promoter of the human MDR1 gene by ras and p53. Science 255:459–462

    PubMed  Google Scholar 

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This study was supported in part by a Grant-Aid for Science and Culture Research from the Ministry of Education, Science and Culture of Japan

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Kurosawa, M., Okabe, M., Kunieda, Y. et al. Analysis of the p53 gene mutations in acute myelogenous leukemia: The p53 gene mutations associated with a deletion of chromosome 17. Ann Hematol 71, 83–87 (1995). https://doi.org/10.1007/BF01699251

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  • DOI: https://doi.org/10.1007/BF01699251

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