Medical Oncology

, Volume 15, Issue 4, pp 248–254 | Cite as

Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration

  • Noriomi Kuribayashi
  • Hiroyuki HataEmail author
  • Hiromitsu Matsuzaki
  • Minoru Yoshida
  • Takashi Sonoki
  • Akitoshi Nagasaki
  • Tatsuya Kimura
  • Naoko Harada
  • Kiyoshi Takatsuki


Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To investigate mechanisms of drug resistance, we generated a monoclonal antibody, clone O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot analysis showed that molecular weight of O3 antigen was approximately 90 kDa. Expression of O3 antigen was approximately two times higher in KHM-11R than in parental melphalan sensitive cell line, KHM-11. O3 was preferentially expressed in plasma cell, B-cell, and monocytic cell lines, but not in T-cell lines. Analysis of bone marrow samples from myeloma patients revealed that 13 of 23 samples expressed O3 antigen at various levels, and that O3 antigen expression in patients correlate with preceding chemotherapy, advanced clinical stage and extramedullar invasion of myeloma cells. Furthermore, patients expressing O3 antigen at the time of diagnosis tended to have poor prognosis. The investigation of O3 antigen in myeloma cells will be useful to reveal the pathophysiology of extramedullar invasion and the mechanism of cell killing by melphalan.


multiple myeloma monoclonal antibody melphalan drug resistance 


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  1. 1.
    Alexanian R, Dimopoulos MA. Management of multiple myeloma.Semin Hematol 1995;32: 20–30.PubMedGoogle Scholar
  2. 2.
    Barlogie B, Jagannath S, Vesole D, Tricot G. Autologus and allogenic transplants for multiple myeloma.Semin Hematol 1995;32: 31–44.PubMedGoogle Scholar
  3. 3.
    Epstein J, Xiao H, Oba BK. P-glycoprotein expression in plasma-cell myeloma is associated with resistance to VAD.Blood 1986;74: 913–917.Google Scholar
  4. 4.
    Mulcahy RT, Bailey HH, Greipp JJ. Up-regulation of gamma-glutamylcysteine synthetase activity in melphalanresistant myeloma cells expressing increased glutathione levels.Cancer Chemother Pharmacol 1994;34: 67–71.PubMedCrossRefGoogle Scholar
  5. 5.
    Bellamy WT, Dalton WS, Gleason MC, Grogan TM, Trent JM. Development and characterization of a melphalanresistant human multiple myeloma cell line.Cancer Res 1991;51: 995–1002.PubMedGoogle Scholar
  6. 6.
    Ishikawa Het al. Expressions of DNA topoisomerase I and II gene and the genes possibly related to drug resistance in human myeloma cells.Br J Haematol 1993;83: 68–74.PubMedGoogle Scholar
  7. 7.
    Anderson KCet al. Antigens on human plasma cells identified by monoclonal antibodies.J Immunol 1983;130: 1132–1138.PubMedGoogle Scholar
  8. 8.
    Huang Net al. Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in adhesion of mature myeloma cells to bone marrow stromal cells.Blood 1993;82: 3721–3729.PubMedGoogle Scholar
  9. 9.
    Hata Het al. Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1.Clin Exp Immunol 1994;96: 370–375.PubMedCrossRefGoogle Scholar
  10. 10.
    Nathan PDet al. An antigen study of human plasma cells in normal tissue and in myeloma: identification of a novel plasma cell associated antigen.Clin Exp Immunol 1986;65: 112–119.PubMedGoogle Scholar
  11. 11.
    Matsuzaki H, Hata H, Takeya M, Takatsuki K. Establishment and characterization of an amylase-producing human myeloma cell line.Blood 1988;72: 978–982.PubMedGoogle Scholar
  12. 12.
    Matsuzaki Het al. Human myeloma cell line (KHM-4) established from a patient with multiple myeloma associated with hyperammonemia.Intern Med 1992;31: 339–343.PubMedGoogle Scholar
  13. 13.
    Hata Het al. Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase.Leukemia 1994;8: 1768–1773.PubMedGoogle Scholar
  14. 14.
    Ohtsuki Tet al. Two human myeloma cell lines, amylase-producing KMS-12-PE and amylase-non-producing KMS-12-BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32).Br J Haematol 1989;73: 199–204.PubMedGoogle Scholar
  15. 15.
    Matsuoka Y, Moore G, Yagi Y, Pressman D. Production of free light chains of immunoglobulin by a hematopoietic cell line derived from a patient with multiple myeloma.Proc Soc Exp Biol Med 1967;125: 1246–1250.PubMedGoogle Scholar
  16. 16.
    Matsuzaki Het al. Establishment and characterization of acute B-cell lymphocytic leukemia cell line showing (8;14) and (14;18) chromosome translocation.Acta Haematol 1990;84: 156–161.PubMedCrossRefGoogle Scholar
  17. 17.
    Sonoki Tet al. Establishment of the novel B acute lymphoblastic leukemia (FAB L3) cell line KHM-10B with a 13q34 abnormality and constitutive expression of c-myc andmax during cell cycle.Leukemia 1995;9: 2093–2099.PubMedGoogle Scholar
  18. 18.
    Epstein MAet al. Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji).J Natl Cancer Inst 1966;37: 547–559.PubMedGoogle Scholar
  19. 19.
    Foley GEet al. Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia.Cancer 1965;18: 522–529.PubMedCrossRefGoogle Scholar
  20. 20.
    Minowada J, Ohnuma T, Moore GE. Rosette-forming human lymphoid cell lines. 1. Establishment and evidence for origin of thymus-derived lymphocytes.J Natl Cancer Inst 1972;49: 891–895.PubMedGoogle Scholar
  21. 21.
    Sandström C, Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U937).Int J Cancer 1976;17: 565–577.CrossRefGoogle Scholar
  22. 22.
    Tsuchiya Set al. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1).Int J Cancer 1980;26: 171–176.PubMedCrossRefGoogle Scholar
  23. 23.
    Grogan TM, Durie BGM, Spier CM, Richter L, Vela E. Myelomonocytic antigen positive multiple myeloma.Blood 1989;73: 763–769.PubMedGoogle Scholar
  24. 24.
    Durie BGMet al. Myelomonocytic myeloma cell line (LB 84-1).Blood 1989;73: 770–776.PubMedGoogle Scholar
  25. 25.
    Kanoh T, Hashitani Y. Phagocytic myeloma cells.Am J Clin Pathol 1986;85: 647.PubMedGoogle Scholar
  26. 26.
    Matsuzaki H, Hata H, Watanabe T, Takeya M, Takatsuki K. Phagocytic multiple myeloma with disseminated intravascular coagulation.Acta Haematol 1989;82: 91–94.PubMedGoogle Scholar

Copyright information

© Stockton Press 1998

Authors and Affiliations

  • Noriomi Kuribayashi
    • 1
  • Hiroyuki Hata
    • 1
    Email author
  • Hiromitsu Matsuzaki
    • 1
  • Minoru Yoshida
    • 1
  • Takashi Sonoki
    • 1
  • Akitoshi Nagasaki
    • 1
  • Tatsuya Kimura
    • 1
  • Naoko Harada
    • 1
  • Kiyoshi Takatsuki
    • 1
  1. 1.Second Department of Internal MedicineKumamoto University School of MedicineKumamotoJapan

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