Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 2, March-April, p. 129–133

Publication type: original article

Language: English

Lack of Association Between CD28 Gene Polymorphism and Multiple Myeloma in a Polish Population

Polimorfizm genu CD28 a ryzyko zachorowania na szpiczaka mnogiego w populacji polskiej

Lidia Karabon1,, Edyta Pawlak1,, Anna Tomkiewicz1,, Marek Kiełbiński1,, Stanisław Potoczek1,, Dariusz Woszczyk2,, Anna Jonkisz3,, Kazimierz Kuliczkowski1,, Irena Frydecka1,4,

1 Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

2 Department of Hematology, State Hospital, Opole, Poland

3 Department of Forensic Medicine, Wroclaw Medical University, Poland

4 Department of Hematology, Neoplastic Diseases, and Bone Marrow Transplantation, Wroclaw Medical University, Poland

Abstract

Background. Immunophenotypic studies revealed that CD28, a T cell−restricted molecule, is expressed on malignant plasma cells and its expression in multiple myeloma (MM) highly correlates with poor prognosis and disease progression, while in normal plasma cells CD28 expression is always absent or only weakly positive in small subsets.
Objectives. As dysregulated expression and/or function of CD28 in myeloma cells may be due to polymorphism of the corresponding gene, this study was undertaken to evaluate the association between CD28c.17 + 3T > C gene polymorphism and multiple myeloma in a Polish population.
Material and Methods. One hundred fifty patients with MM and 238 healthy subjects were examined. The T > C transition at position 17 in intron 3 of the CD28 gene was genotyped by polymerase chain reaction followed by labeling with a SNaPshot kit and detected using a capillary genetic analyzer.
Results. The genotype, allele, and phenotype frequencies did not significantly differ between MM patients and controls.
Conclusion. The present study was unable to reveal any association between CD28c.17 + 3T > C gene polymorphism and the risk of multiple myeloma in a Polish population.

Streszczenie

Wprowadzenie. Badania immunofenotypowe wykazały, że CD28, molekuła, której ekspresję stwierdza się głównie na powierzchni limfocytów T, jest również obecna na nowotworowych komórkach plazmatycznych. Jej ekspresja na nowotworowych plazmocytach w szpiczaku plazmocytowym wykazuje silny związek ze złym rokowaniem i progresją choroby. Prawidłowe komórki plazmatyczne zwykle nie ekspresjonują cząsteczki CD28, chociaż słabą ekspresję tej molekuły czasem obserwuje się na powierzchni niewielkiej frakcji tych komórek.
Cel pracy. Zaburzenia ekspresji lub/i funkcji CD28 na nowotworowych komórkach plazmatycznych mogą być spowodowane polimorfizmem odpowiedniego genu. Celem pracy było zbadanie zależności między polimorfizmem genu CD28 a ryzykiem zachorowania na szpiczaka plazmocytowego w polskiej populacji.
Materiał i metody. Badania przeprowadzono u 150 chorych na szpiczaka plazmocytowego i 238 zdrowych osób. Wymiana T > C w pozycji 17 w intronie 3 była genotypowana z użyciem reakcji PCR. Następnie produkty PCR znakowano techniką SNaPshot i identyfikowano z użyciem sekwenatora kapilarnego.
Wyniki. Częstość występowania poszczególnych genotypów, alleli i fenotypów nie różniła się między grupą chorych na szpiczaka plazmocytowego i grupą kontrolną.
Wnioski. Polimorfizm c.17 + 3T > C genu CD28 nie jest czynnikiem ryzyka zachorowania na szpiczaka plazmocytowego w populacji polskiej.

Key words

multiple myeloma, costimulatory molecule CD28, gene polymorphism

Słowa kluczowe

szpiczak mnogi, molekuła kostymulująca CD28, polimorfizm genu

References (24)

  1. Kozbor D, Moretta A, Messner HA, Croce CM: Tp44 molecules involved in antigen independent T cell activation are expressed on human plasma cells. J Immunol 1987, 138, 4128–4132.
  2. Zhang X−G, Gaillard JP, Robillard N, Lu ZY, Gu ZJ, Jourdan M, Boiron JM, Bataille R, Klein B: Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. Blood 1994, 83, 3654–3663.
  3. Pellat−Deceunynck C, Bataille R, Robillard N, Harousseau J−L, Rapp M−J, Juge−Morineau N, Wijdenes J, Amiot M: Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 1994, 84, 2597–2603.
  4. Mateo G, Castellanos M, Rasillo A, Gutierrez NC, Montalban MA, Martin ML, Hernandez JM, Lopez−Berges MC, Montejano L, Blade J, Mateos MV, Sureda A, de la Rubia J, Diaz−Mediavilla J, Pandiella A, Lahuerta JJ, Orfao A, San Miguel JF: Genetic abnormalities and patterns of antigenic expression in multiple myeloma. Clin Cancer Res 2005, 11, 3661–3667.
  5. Robillard N, Jego G, Pellat−Deceunynck C, Pineau D, Puthier D, Mellerin MP, Barillé S, Rapp MJ, Harousseau JL, Amiot M, Bataille R: CD28, a marker associated with tumoral expansion in multiple myeloma. Clin Cancer Res 1998, 4, 1521–1526.
  6. Westendorf JJ, Ahmann GJ, Greipp PR, Witzig TE, Lust JA, Jelinek DF: Establishment and characterization of three myeloma cell lines that demonstrate variable cytokine responses and abilities to produce interleukin−6. Leukemia 1996, 10, 866–876.
  7. Shapiro VS, Mollenauer MN, Weiss A: Endogenous CD28 expressed on myeloma cells up−regulates interleukin−8 production: implications for multiple myeloma progression. Blood 2001, 98, 187–193.
  8. Frauwirth KA, Thompson CB: Activation and inhibition of lymphocytes by costimulation. J Clin Invest 2002, 109, 295–299.
  9. Bahlis NJ, King AM, Kolonias D, Carlson LM, Liu HY, Hussein MA, Terebelo HR, Byrne GE Jr, Levine BL, Boise LH, Lee KP: CD28−mediated regulation of multiple myeloma cell proliferation and survival. Blood 2007, 109, 5002–5010.
  10. Qiu YH, Sun ZW, Shi Q, Su CH, Chen YJ, Shi YJ, Tao R, Ge Y, Zhang XG: Apoptosis of multiple myeloma cells induced by agonist monoclonal antibody against human CD28. Cell Immunol 2005, 236, 154–160.
  11. Greipp PR, San Miguel J, Durie BGM, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet−Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonnenveld P, Tosi P, Turesson I, Westein J: International staging system for multiple myeloma. J Clin Oncol 2005, 23, 3412–3420.
  12. Bocko D, Kosmaczewska A, Ciszak L, Teodorowska R, Frydecka I: CD28 costimulatory molecule−expression, structure and function. Arch Immunol Ther Exp 2002, 50, 169–177.
  13. Heinzmann A, Plesnar C, Kuehr J, Forster J, Deichmann KA: Common polymorphism in the CTLA−4 and CD28 genes at 2q33 are not associated with asthma or atopy. Eur J Immunogenet 2000, 27, 57–61.
  14. Tomer Y, Greenberg DA, Barbesino G, Concepcion E, Davies TF: CTLA−4 and not CD28 is susceptibility gene for thyroid autoantibody production. J Clin Endocrinol Metab 2001, 86, 1687–1693.
  15. Ahmed S, Ihara K, Kanemitsu S, Nakashima H, Otsuka T, Tsuzaka K, Takeuchi T, Hara T: Association of CTLA−4 but not CD28 gene polymorphisms with systemic lupus erythematous in the Japanese population. Rheumatology (Oxford) 2001, 40, 662–667.
  16. Van Veen T, Crusius JBA, Winsen L, Xia B, Barkhof F, Pena AS, Polman CH, Uitdehaag BMJ: CTLA−4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis. J Neuroimmunol 2003, 140, 188–193.
  17. Djilali−Saiah I, Quellete P, Caillat−Zucman S, Debray D, Kohn JI, Alvarez F: CTLA−4CD/28 region polymorphisms in children from families with autoimmune hepatitis. Hum Immunol 2001, 62, 1356–1362.
  18. Ihara K, Ahmed S, Nakao F, Kinukawa N, Kuromaru R, Matsuura N, Iwata I, Nagafuchi S, Kohno H, Miyako K, Hara T: Association studies of CTLA−4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population. Immunogenetics 2001, 53, 447–454.
  19. Heinzmann A, Plesnear C, Kueher J, Forster J, Deichmann KA: Lack of association between CD28/CTLA−4 gene polymorphisms and atopic asthma in or atopy. Eur J Immunogenet 2000, 27, 57–61.
  20. Nakao F, Ihara K, Amed S, Sasaki Y, Kusuhara K, Takabayashi A, Nishima S, Hara T: Lack of association between CD28/CTLA−4 gene polymorphisms and atopic asthma in the Japanese population. Exp Clin Immunogenet 2000, 17, 179–184.
  21. Cheng TY, Lin JT, Chen LT, Shun CT, Wang HP, Lin MT, Wang TE, Cheng AL, Wu MS: Association of T−cell regulatory gene polymorphisms with susceptibility to gastric mucosa−associated lymphoid tissue lymphoma. J Clin Oncol 2006, 24, 3483–3489.
  22. Włodarska−Polińska I, Pawlak E, Suwalska K, Dobosz T, Potoczek S, Kornafel J, Frydecka I: Lack of association between CD28 gene polymorphism and cervical cancer in Lower Silesia population. Adv Clin Exp Med 2006, 15, 595–594.
  23. Guzman VB, Yambartsev A, Goncalves−Primo A, Silva ID, Carvalho CR, Ribalta JC, Goulart LR, Shulzhenko N, Gerbase−Delima M, Morgun A: New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer. Hum Mol Genet 2008, 17, 1838–1844.
  24. Suwalska K, Pawlak E, Karabon L, Tomkiewicz A, Dobosz T, Urbaniak−Kujda D, Kuliczkowski K, Wolowiec D, Jedynak A, Frydecka I: Association studies of CTLA−4, CD28, and ICOS gene polymorphisms with B−cell chronic lymphocytic leukemia (B−CLL) in the Polish population. Hum Immunol 2008, 69, 193–201.
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