Expression of PRAME gene in multiple myeloma


Cite item

Full Text

Abstract

Aim. To determine clinical significance of PRAME gene expression in multiple myeloma (MM) and feasibility of its use as a marker of residual tumor clone.
Material and methods. 35 MM patients, of them 15 were newly diagnosed and 20 had resistance to previous therapy. PRAME was made if the patients received programmed therapy with high-dose chemotherapy (VD) and autologous transplantation of peripheral cell stem cells. 12 PRAME-positive patients were examined on the day +100, 5 patients ~ a year later. Monoclonal paraprotein was detected by electrophoresis and radial immunodiffusion of blood serum. Bone marrow affection was assessed at roentgenography and/or MRI. PRAME gene expression in bone marrow biopsy was measured by reverse transcription and PCR amplification.
Results. Activation of expression of PRAME gene in MM was found in 68.57% patients. It was higher in patients with MM duration more than 1 year and if they were treated before (85%) than in new cases (46.67%). Expression of PRAME tended to associate with activity of LDP of blood serum. After the above chemotherapy and autotransplantation transcript PRAME did not disappear in 8 of 12 cases. One year after the treatment, of 5 PRAME-positive patients 2 died, 1 had recurrence, 2 are in a compete clinicohematologica/ remission.
Conclusion. Frequent activation of transcription of the gene FRAME in MM, its assay can be used for monitoring of the disease course, assessment of remission completeness, detection of tumor cell contamination of preparations of autologous stem cells of peripheral blood.

References

  1. Boon Т., Cerattini J.-C., van den Eynde В.,van den Bruggen P. Tumor antigens recognized by T lymphocytes. Annu. Rev. Immunol. 1994; 12 (4): 337-365.
  2. Ikeda В., Matsushita M., Kawakami H. PRAME protein expressed in leukemia cells as a target molecule for immunotherapy. Rinsho Ketsueki 1999; 40 (6): 484-486.
  3. Kirkin A. F., Dzhandrhugazyan K., Zeuthen J. The immunogenic properties of melanoma-associated antigens recognized by cytotoxic T lymphocytes. Exp. Clin. Immunogenet. 1998; 15 (1): 19-32.
  4. Pellat-Deceunynck C., Mellerin M. P., Labarriere N. et al. The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells. Eur. J. Immunol. 2000; 30 (6): 803-809.
  5. Steinbach D., Viehmann S., Zintl F., Gruhn B. PRAME gene expression in childhood acute lymphoblastic leukemia. Cancer Genet. Cytogenet. 2002; 138 (1): 89-91.
  6. Steinbach D., Hermann J., Viehmann S. et al. Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Ibid. 2002; 133 (2): 118-123.
  7. van Baren N., Brasseur F., Godelaine D. et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood 1999; 94 (4): 1156-1164.
  8. Durie B. G. M., Salmon S. E. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer (Philad.) 1975; 36 (10): 842-854.
  9. Chomczynski P., Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt. Biochem. 1987; 162 (1): 156-159.
  10. Watari K., Top A., Nagamura-Inoue T. et al. Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene. FEBS Lett. 2000; 466 (2-3): 367-371.
  11. Matsushita M., Ikeda H., Kizaki M. et al. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br. J. Haematol. 2001; 112 (4): 916- 926.
  12. Gilliland D. G. Molecular genetics of human leukemias: New insights into therapy. Semin. Hematol. 2002; 39 (4, suppl. 3): 6-11.
  13. Suguro M., Kanda Y., Yamamoto R. et al. High serum lactate dehydrogenase level predicts short survival after vincristinedoxorubicin- dexamethasone (VAD) salvage for refractory multiple myeloma. Am. J. Hematol. 2000; 65 (2): 132-135.
  14. Knechti Ch. J. C., Goulden N. J., Grandage V. L. G. et al. Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia. Blood 1998; 92 (10): 4072-4079.
  15. Stewart A. K., Vescio R., Schiller G. et al. Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J. Clin. Oncol. 2001; 19 (17): 3771-3779.
  16. Sugimoto Т., Das H., Imoto S. et al. Quantitation of minimal residual disease in t(8; 21)-positive acute myelogenous leukemia patients using real-time quantitative RT-PCR. Am. J. Hematol. 2000; 64 (2): 101-106.
  17. Lopez-Perez R., Garcia-Sanz R., Gonzalez D. et al. Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 2001; 28 (7): 665-672.
  18. Kessler J. H., Beekman N. J., Bres-Vloemans S. A. et al. Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis. J. Exp. Med. 2001; 193 (1): 73-88.
  19. The Myeloma Trialists' Collaborative Group. Iterferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br. J. Haematol. 2001; 113 (4): 1020-1034.
  20. Kyle R. A. Management of patients with multiple myeloma: emphasizing the role of high-dose therapy. Clin. Lymphoma 2001; 2(1): 21-28.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2004 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies