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1998 Fiscal Year Final Research Report Summary

Oncogenesis of Human Myeloma and Altered Expression of Pax-5 gene

Research Project

Project/Area Number 09671115
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionYamaguchi University

Principal Investigator

KAWANO Michio  Faculty of Medicine, Yamaguchi University Professor, 医学部, 教授 (40161343)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Hideaki  Faculty of Medicine, Yamaguchi University Associate Professor, 医学部, 助教授 (40294623)
Project Period (FY) 1997 – 1998
KeywordsMyeloma / Pax-5 / Methylation / CD19 / Gene transfer / Transcription factor / Myeloma cell / SCID mouse
Research Abstract

In order to clarify the mechanism of oncogenesis of human myeloma, we isolated and cloned 5' upstream region of human Pax-5 gene that is specifically lost in myeloma cells. We investigated the structural abnormality of Pax-5 gene in human myeloma cell lines and primary myeloma cells from myeloma patients. Also, we examined the biological significance of loss of CD19 in myeloma cell lines by introduction of CD19 gene expression into these cell lines. Neither rnyeloma cell lines nor primary myeloma cell showed any structural abnormality of Pax-5 gene including 5' upstream region. However, within 4 kb upstream region of Pax-5 gene, CpG sites were hypermethylated in myeloma ceIl lines and primary myeloma cells compared with Pax-5-positive B cell lines. Furthermore, treatment of myeloma cell lines with azadeoxycytidine recovered their expression of Pax- 5 gene. These results suggest that loss of Pax-5 expression in myeloma cells may be derived from hypermethylation of upstream regulatory region of Pax-5 gene. Another interesting finding was obtained transfection of CD19 gene into myeloma cell lines showed marked reduction of their proliferation both in vitro and in SCID mice. This suggests that loss of CD19 expression in myeloma cells is not merely the result from loss of Pax-5 gene expression but makes sense of acquisition of growth advantage during oncogenesis. In conclusion, in this project, we obtained fruitful results that altered expression of P ax-5 gene is closely associated with onco genesis of human myeloma.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kawano, M.M.: "Cyclin D1 and p16^<INK4A> are preferentially expressed in immature and mature myeloma cells, respectively." Br.J.Haematol.99・1. 131-138 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mahmoud, M.S.: "Induction of CD45 expression and proliferation in U-266 myeloma cell line by interleukin-6." Blood. 92・10. 3887-3897 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishikawa, H.: "Biological significance of heterogeneity in human myeloma cells." Int.J.Hematol.68・4. 363-370 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujii, R.: "MPC-1-CD49e- immature myeloma cells include CD45+subpopulations that can proliferate in response to IL-6 in human myeloma cells." Br.J.Haematol.105 in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石川 秀明: "形質細胞の腫瘍化とPax-5遺伝子" 血液・腫瘍科. 36・5. 440-448 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石川 秀明: "Pax-5とB細胞の分化" アレルギー科. 6・1. 63-69 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河野 道生(分担): "最新内科学大系 プログレス3" 中山書店, 13 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河野 道生(分担): "Annual Review 血液" 中外医学社, 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawano, M.M.: "Cyclin D1 and p16^<INK4A> are preferentially expressed in immature and mature myeloma cells, respectively." Br.J.Haematol.99・1. 131-138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mahmoud, M.S.: "Induction of CD45 expression and proliferation in U-266 myeloma cell line by interleukin-6." Blood. 92・10. 3887-3897 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa, H.: "Biological significance of heterogeneity in human myeloma cells." Int.J.Hematol.68・4. 363-370 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujii, R.: "MPC-1-CD49e- immature myeloma cells include CD45+ subpopulations that can proliferate in response to IL-6 in human myeloma cells." Br.J.Haematol.105 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa, H.: "Oncogenesis of plasma cell and Pax-5 gene (in Japanese)" Hematology & Oncology. 36・5. 440-448 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa, H.: "Pax-5 and B cell differentiation (in Japanese)" Allergy. 6・1. 63-69 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawano, MM.: Integrated Handbook of Internal Medicine Progress 3.Hematology (in Japanese). Nakayama-Shoten, 13 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawano, MM.: Annual Review Hematology (in Japanese). Chugai-Igaku, 6 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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