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IFN Gamma Gene Polymorphism May Contribute to the Susceptibility to CLL

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Pathology & Oncology Research

Abstract

The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked with the production and activity of certain growth factors. However a significant proportion of CLL patients display immune abnormalities suggestive of aberrant cytokine secretion and/or response. In contrast to B lymphocytes, T cells of B-CLL patients characterise with the increased production of interferon-gamma (IFN-γ) and this cytokine has been indicated to prevent malignant cells from entering apoptosis including the slowly expanding population of CD5+ B cells that characterizes chronic lymphocytic leukemia. The aim of the present study was to assess whether functionally relevant interferon-gamma gene (IFNG) polymorphism (+847 A/T) contributes to the pathogenesis of B-CLL. In total 110 individuals was investigates, including 61 CLL patients and 50 healthy individuals. The presence of the IFNG AA genotype was found to be associated with susceptibility to CLL (23/61 vs. 7/50, p < 0.005, for patients and controls, respectively). This results suggest that individuals rather prone to the lower level of IFN-γ production (associated with the presence of the A allele) appear to be more susceptible to this malignant disease.

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References

  1. Abbott BL (2004) Advances in the diagnosis and treatment of chronic lymphocytic leukemia. Clin Adv Hematol Oncol 2:448–454

    PubMed  Google Scholar 

  2. Zenz T, Mertens D, Dohner H, Stilgenbauer S (2008) Molecular diagnostics in chronic lymphocytic leukemia—Pathogenetic and clinical implications. Leuk Lymphoma 15:1–10

    Google Scholar 

  3. Mainou-Fowler T, Prentice AG (1996) Modulation of apoptosis with cytokines in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 21:369–377

    Article  CAS  PubMed  Google Scholar 

  4. Pravica V, Perrey C, Stevens A et al (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61:863–866

    Article  CAS  PubMed  Google Scholar 

  5. Pravica V, Asderakis A, Perrey C et al (1999) In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur J Immunogenet 26:1–3

    Article  CAS  PubMed  Google Scholar 

  6. Perrey C, Pravica V, Sinnott PJ, Hutchinson IV (1998) Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol 6:193–197

    Article  CAS  PubMed  Google Scholar 

  7. Bogunia-Kubik K, Mazur G, Urbanowicz I, Wróbel T, Kuliczkowski K, Woźniak M, Lange A (2006) Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukemia. Int J Immunogenet 33:21–24

    Article  CAS  PubMed  Google Scholar 

  8. Kiaii S, Choudhury A, Mozaffari F, Rezvany R, Lundin J, Mellstedt H, Osterborg A (2006) Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia: long-term effects of fludarabine and alemtuzumab treatment. Leuk Lymphoma 47:1229–1238

    Article  CAS  PubMed  Google Scholar 

  9. Kiaii S, Choudhury A, Mozaffari F, Kimby E, Osterborg A, Mellstedt H (2005) Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia (B-CLL): comparison of indolent and progressive disease. Med Oncol 22:291–302

    Article  CAS  PubMed  Google Scholar 

  10. Rossmann ED, Lewin N, Jeddi-Tehrani M, Osterborg A, Mellstedt H (2002) Intracellular T cell cytokines in patients with B cell chronic lymphocytic leukaemia (B-CLL). Eur J Haematol 68:299–306

    Article  CAS  PubMed  Google Scholar 

  11. Podhorecka M, Dmoszynska A, Rolinski J (2004) Intracellular IFN-gamma expression by CD3+/CD8+ cell subset in B-CLL patients correlates with stage of the disease. Eur J Haematol 73:29–35

    Article  CAS  PubMed  Google Scholar 

  12. Totero D, Tazzari PL, Capaia M, Montera MP, Clavio M, Balleari E, Foa R, Gobbi M (2003) CD40 triggering enhances fludarabine-induced apoptosis of chronic lymphocytic leukemia B-cells through autocrine release of tumor necrosis factor-alpha and interferon-gama and tumor necrosis factor receptor-I-II upregulation. Haematologica 88:148–158

    PubMed  Google Scholar 

  13. Gallego A, Vargas JA, Castejón R, Citores MJ, Romero Y, Millán I, Durántez A (2003) Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL. Cytometry B Clin Cytom 56:23–29

    Article  CAS  PubMed  Google Scholar 

  14. Warle MC, Farhan A, Metselaar HJ et al (2003) Are cytokine gene polymorphisms related to in vitro cytokine production profiles? Liver Transpl 9:170–181

    Article  PubMed  Google Scholar 

  15. Vandenbroeck K, Goris A (2003) Cytokine gene polymorphisms in multifactorial diseases: gateways to novel targets for immunotherapy? Trends Pharmacol Sci 24:284–289

    Article  CAS  PubMed  Google Scholar 

  16. Zaki M, Douglas R, Patten N, Bachinsky M, Lamb R, Nowell P, Moore J (2000) Disruption of the IFN-gamma cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis. Leuk Res 24:611–621

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Chemistry, Wroclaw Medical University, Pasteur 2 Str, 50-367, Wroclaw, Poland

    Iwona Urbanowicz, Jolanta Stacherzak-Pawlik & Mieczysław Woźniak

  2. Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland

    Grzegorz Mazur, Tomasz Wróbel & Kazimierz Kuliczkowski

  3. Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

    Katarzyna Bogunia-Kubik

Authors
  1. Iwona Urbanowicz
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  2. Grzegorz Mazur
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  3. Jolanta Stacherzak-Pawlik
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  4. Katarzyna Bogunia-Kubik
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  5. Tomasz Wróbel
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  6. Mieczysław Woźniak
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  7. Kazimierz Kuliczkowski
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Correspondence to Iwona Urbanowicz.

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Urbanowicz, I., Mazur, G., Stacherzak-Pawlik, J. et al. IFN Gamma Gene Polymorphism May Contribute to the Susceptibility to CLL. Pathol. Oncol. Res. 16, 213–216 (2010). https://doi.org/10.1007/s12253-009-9209-2

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  • DOI: https://doi.org/10.1007/s12253-009-9209-2

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