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MAGE-C1 gene and mage-c1 protein expression comparison in primary multiple myeloma patients

https://doi.org/10.17650/1818-8346-2022-17-2-51-59

Abstract

Background. Nowadays, hematology is a dynamically developing science due to the in-depth study of the molecular mechanisms of a particular disease. A better understanding of oncohematological diseases biology makes it possible to synthesize new targeted drugs, which have a favorable therapeutic effect. In particular, in multiple myeloma, after the introduction of proteasome inhibitors and immunomodulatory drugs into clinical practice, an improvement in overall survival was observed. However, characteristics of the mechanisms of transformation normal plasma cells into malignant ones are still difficult; therefore, the study of the pathobiological basis of multiple myeloma is currently an urgent task.
The objective: to evaluate the possible influence of MAGE-C1 gene expression and the presence of mage-c1 protein in patients with newly diagnosed multiple myeloma on the anti-tumor response after bortezomib-containing therapy.
Materials and methods. A prospective study included 33 multiple myeloma patients. The diagnosis was established according to International Myeloma Working Group criteria (IMWG, 2014). In 32 patients the induction therapy included bortezomib-containing courses, in one patient lenalidomide was included in the first-line regimens. The MAGE-C1 gene expression by real-time polymerase chain reaction and mage-c1 protein by immunohistochemistry in plasma cells bone marrow, were determined for all patients at the debut of multiple myeloma. As a control group was examined the bone marrow material of healthy donors.
Results. When assessment the statistical relationship between the expression of MAGE-C1 gene and mage-c1 protein, it was found that there was no high expression of mage-c1 protein at low values of MAGE-C1 gene expression. At the same time, high expression of the gene was always associated with protein expression above normal values. The analysis aimed at finding the relationship between MAGE-C1 gene and mage-c1 protein detection and the degree of antitumor response after 6 courses of induction therapy showed that high expression of the studied parameters was associated with a worse response to bortezomib-containing treatment.
Conclusion. We confirmed that the results of the two methods were comparable. Single factor analysis showed that patients with decreased MAGE-C1 gene and mage-c1 protein expression levels achieved a significantly higher antitumor response to bortezomib-containing regimens, while high expression was accompanied by refractoriness to bortezomib.

About the Authors

E. A. Makunina
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



L. P. Mendeleeva
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



V. L. Surin
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



M. V. Soloviev
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



M. V. Firsova
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



A. M. Kovrigina
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



A. A. Sherstnev
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



I. V. Gal’tseva
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



Y. O. Davydova
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



S. M. Kulikov
National Research Center for Hematology, Ministry of Health of Russia
Russian Federation

125167, Moscow, Novyy Zykovskiy Proezd, 4



References

1. Kryukov F., Nemec P., Radova L. et al. Centrosome associated genes pattern for risk sub-stratification in multiple myeloma. J Transl Med 2016;14(1):150. DOI:10.1186/s12967-016-0906-9.

2. Prideaux S.M., Conway O’Brien E., Chevassut T.J. The genetic architecture of multiple myeloma. Adv Нematol 2014;2014:864058. DOI:10.1155/2014/864058.

3. Morgan G.J., Walker B.A., Davies F.E. The genetic architecture of multiple myeloma. Nat Rev Cancer 2012;12(5):335–48. DOI:10.1038/nrc3257.

4. Landgren O., Iskander K. Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes. J Intern Med 2017;281(4):365–82. DOI:10.1111/joim.12590.

5. Cavo M., Rajkumar S.V., Palumbo A. et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood 2011;117(23):6063–73. DOI:10.1182/blood-2011-02-297325.

6. Shires K., van Wyk T. The role of cancer/ testis antigens in multiple myeloma pathogenesis and their application in disease monitoring and therapy. Crit Rev Oncol Hematol 2018;132:17–26. DOI:10.1016/j.critrevonc.2018.09.010.

7. Simpson A.J.G. Caballero O.L., Jungbluth A. et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005;5(8):615–25. DOI:10.1038/nrc1669.

8. Zhang Y., Bao L., Lu J. et al. The clinical value of the quantitative detection of four cancer-testis antigen genes in multiple myeloma. Mol Сancer 2014;13(1):25. DOI:10.1186/1476-4598-13-25.

9. De Carvalho F., Vettore A.L., Colleoni G.W.B. Cancer/testis antigen MAGE-C1/CT7: new target for multiple myeloma therapy. Clin Develop Immunol 2012;2012:257695. DOI:10.1155/2012/257695.

10. De Carvalho F., Alves V.L.F., Braga W.M.T. et al. MAGE-C1/CT7 and MAGE-C2/CT10 are frequently expressed in multiple myeloma and can be explored in combined immunotherapy for this malignancy. Cancer Immunol Immunother 2013;62(1):191–5. DOI:10.1007/s00262-012-1376-4.

11. Andrade V.C.C., Vettore A.L., Felix R.S. et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun 2008;8:2.

12. Scanlan M.J., Andrew J.G., Old L.J. The cancer/testis genes: review, standardization, and commentary. Cancer Immun 2004;4(1):1.

13. Lim S.H., Austin S., Owen-Jones E. et al. Expression of testicular genes in haematological malignancies. Br J Cancer 1999;81(7):1162–4. DOI:10.1038/sj.bjc.6690824.

14. Jungbluth A.A., Ely S., Di Liberto M. et al. The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation. Blood 2005;106(1):167–74. DOI:10.1182/blood-2004-12-4931.

15. Wienand K., Shires K. The use of MAGE C1 and flow cytometry to determine the malignant cell type in multiple myeloma. PloS One 2015;10(3):e0120734. DOI:10.1371/journal.pone.0120734.

16. He L., Ji J., Liu S. et al. Expression of cancer-testis antigen in multiple myeloma. J Huazhong Univ Sci Technolog Med Sci 2014;34(2):181–5. DOI:10.1007/s11596-014-1255-7.

17. Rajkumar S.V., Dimopoulos M.A., Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma Lancet Oncol 2014;15(12):е538–48. DOI:10.1016/S1470-2045(14)70442-5.

18. Atanackovic D., Luetkens T., Hildebrandt Y. et al. Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma. Clin Cancer Res 2009;15(4):1343–52. DOI:10.1158/1078-0432.ccr-08-098.9.

19. Tyler E.M., Jungbluth A.A., Gnjatic S. et al. Cancer-testis antigen 7 expression and immune responses following allogeneic stem cell transplantation for multiple myeloma. Cancer Immunol Res 2014;2(6):547–58. DOI:10.1158/2326-6066.cir-13-0174.

20. Condomines M., Hose D., Raynaud P. et al. Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis. J Immunol 2007;178(5):3307–15. DOI:10.4049/jimmunol.178.5.3307.

21. Van Duin M., Broyl A., de Knegt Y. et al. Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy. Haematologica 2011;96(11):1662–9. DOI:10.3324/haematol.2010.037978.

22. Tinguely M., Jenni B., Knights A. et al. MAGE-C1/CT-7 expression in plasma cell myeloma: sub-cellular localization impacts on clinical outcome. Cancer Sci 2008;99(4):720–5. DOI:10.1111/j.1349-7006.2008.00738.

23. De Carvalho F., Costa E.T., Camargo A.A. et al. Targeting MAGE-C1/CT7 expression increases cell sensitivity to the proteasome inhibitor bortezomib in multiple myeloma cell lines. PloS One 2011;6(11):e27707. DOI:10.1371/journal.pone.0027707.


Review

For citations:


Makunina E.A., Mendeleeva L.P., Surin V.L., Soloviev M.V., Firsova M.V., Kovrigina A.M., Sherstnev A.A., Gal’tseva I.V., Davydova Y.O., Kulikov S.M. MAGE-C1 gene and mage-c1 protein expression comparison in primary multiple myeloma patients. Oncohematology. 2022;17(2):51-59. (In Russ.) https://doi.org/10.17650/1818-8346-2022-17-2-51-59

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ISSN 1818-8346 (Print)
ISSN 2413-4023 (Online)