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Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels

  • Rezai, Omran (Department of Immunology, Petroleum and Environmental Pollutants Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Khodadadi, Ali (Department of Immunology, Petroleum and Environmental Pollutants Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Heike, Yuji (Immunotherapy and Cell Therapy Service, St Luke's International University and Hospital) ;
  • Mostafai, Ali (Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences) ;
  • Gerdabi, Nader Dashti (Department of Immunology, Petroleum and Environmental Pollutants Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Rashno, Mohammad (Department of Immunology, Petroleum and Environmental Pollutants Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Abdoli, Zahra (Department of Immunology, Petroleum and Environmental Pollutants Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences)
  • Published : 2015.11.04

Abstract

Background: Leukemia is a common cancer among children and adolescents. Wilms' tumor gene (WT1) is highly expressed in patients with acute leukemia. It is found as a tumor associated antigen (TAA) in various types of hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). In this regard, WT1 is a transcription factor that promotes gene activation or repression depending on cellular and promoter context. The purpose of this study was assessment of WT1 gene expression in patients with acute leukemia, measurement of IL-12 and C3 levels in serum and evaluation of the relationship between them. Materials and Methods: We evaluated the expression of WT1 mRNA using real-time quantitative RT-PCR and serum levels of IL-12 and C3 using ELISA and nephelometry in peripheral blood of 12 newly diagnosed patients with acute leukemia and 12 controls. Results: The results of our study showed that the average wT1 gene expression in patients was 7.7 times higher than in healthy controls (P <0.05). In addition, IL-12 (P = 0.003) and C3 (P <0.0001) were significantly decreased in the test group compared to controls. Conclusions: WT1 expression levels are significantly higher in patients compared with control subjects whereas serum levels of interleukin-12 and C3 are significantly lower in patients. Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3.

Keywords

Acute leukemia;C3;interleukin-12;Wilms tumor gene expression

References

  1. A M (2012). Mesdaghinia. Reporting of cancer cases registered in 2008 and 2009 , Tehran - Iran. Cancer office, center for non-communicable diseases, department of health management 2012.(Presian)
  2. Abbas AK, Andrew HL, Shiv P (2007). Cellular and molecular immunology. Sixth edition, SaundersElsevier, 580-618.
  3. Brieger J, Weidmann E, Fenchel K, et al (1994). The expression of the Wilms’ tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells. Leukemia, 8, 2138-43.
  4. Caldon C, Lee C, Sutherland R, et al (2008). Wilms’ tumor protein 1: an early target of progestin regulation in T-47D breast cancer cells that modulates proliferation and differentiation. Oncogene, 27, 126-38. https://doi.org/10.1038/sj.onc.1210622
  5. Carter BZ, Milella M, Altieri DC, et al (2001). Cytokineregulated expression of survivinin myeloid leukemia. Blood, 97, 2784-90. https://doi.org/10.1182/blood.V97.9.2784
  6. Chiusa L, di Celle PF, Campisi P, et al (2006). Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute lymphoblastic leukemia. haematologica, 91, 270-1.
  7. Ferretti E, Di Carlo E, Cocco C, et al (2010). Direct inhibition of human acute myeloid leukemia cell growth by IL-12. Immunology letters, 133, 99-105. https://doi.org/10.1016/j.imlet.2010.08.002
  8. Iranparast S, Assarehzadegan M-A, Heike Y, et al (2014). Wilms' tumor gene (WT1) expression correlates with vascular epithelial growth factor (VEGF) in newly acute leukemia patients undergoing chemotherapy. Asian Pac J Cancer Prev, 15, 9217-23 https://doi.org/10.7314/APJCP.2014.15.21.9217
  9. Jemal A, Siegel R, Ward E, et al (2008). Cancer statistics, 2008. CA: A Cancer J Clin, 58, 71-96. https://doi.org/10.3322/CA.2007.0010
  10. Jurianz K, Ziegler S, Garcia-Schüler H, et al (1999). Complement resistance of tumor cells: basal and induced mechanisms. Molecular Immunol, 36, 929-39. https://doi.org/10.1016/S0161-5890(99)00115-7
  11. Kletzel M, Olzewski M, Huang W, et al (2002). Utility of WT1 as a reliable tool for the detection of minimal residual disease in children with leukemia. Pediatric and Developmental Pathology, 5, 269-75. https://doi.org/10.1007/s10024-001-0208-x
  12. Lee SB, Haber DA (2001). Wilms tumor and the WT1 gene. Experimental Cell Res, 264, 74-99. https://doi.org/10.1006/excr.2000.5131
  13. Mayo MW, Wang CY, Drouin SS, et al (1999). WT1 modulates apoptosis by transcriptionally upregulating the bcl-2 protooncogene. The EMBO J, 18, 3990-4003. https://doi.org/10.1093/emboj/18.14.3990
  14. Menssen H, Renkl H-J, Rodeck U, et al (1995). Presense of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia, 9, 1060-7.
  15. Miyagi T, Ahuja H, Kubota T, et al (1993). Expression of the candidate Wilm’s tumor gene, WT1, in human leukemia cells. Leukemia, 7, 970-7.
  16. Morrison AA, Ladomery MR (2006). Presence of WT1 in nuclear messenger RNP particles in the human acute myeloid leukemia cell lines HL60 and K562. Cancer letters, 244, 136-41. https://doi.org/10.1016/j.canlet.2005.12.018
  17. Nakajima H, Oka Y, Tsuboi A, et al (2015). Enhancement of efficacy of wilms' tumor gene WT1 Product-derived peptide cancer vaccine by co-administration with immunopotentiating agents: lessons from mouse models. in 'inflammation and immunity in cancer', Eds Springer, 165-83
  18. O'Hara RJ, Greenman J, MacDonald AW, et al (1998). Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production. Clin Cancer Res, 4, 1943-8.
  19. Oka Y, Tsuboi A, Taguchi T, et al (2004). Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proceedings of the National Academy of Sciences of the United States of America, 101, 13885-90.
  20. Okroj M, Hsu Y-F, Ajona D, et al (2008). Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors. Molecular Immunol, 45, 169-79. https://doi.org/10.1016/j.molimm.2007.04.025
  21. Opal SM, DePalo VA (2000). Anti-inflammatory cytokines. Chest Journal, 117, 1162-72. https://doi.org/10.1378/chest.117.4.1162
  22. Pegram H, Purdon T, van Leeuwen D, et al (2014). IL-12- secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia. Leukemia, 1-8.
  23. Pio R, Corrales L, Lambris JD (2014). The role of complement in tumor growth. In 'Tumor Microenvironment and Cellular Stress', Eds Springer, 229-62
  24. Pritchard-Jones K, Fleming S, Davidson D, et al (1990). The candidate Wilms’ tumour gene is involved in genitourinary development. Nature, 346, 194-7. https://doi.org/10.1038/346194a0
  25. Rosenfeld C, Cheever M, Gaiger A (2003). WT1 in acute leukemia, chronic myelogenous leukemia and myelodysplastic syndrome: therapeutic potential of WT1 targeted therapies. Leukemia, 17, 1301-12. https://doi.org/10.1038/sj.leu.2402988
  26. Ryningen A, Wergeland L, Glenjen N, et al (2005). In vitro crosstalk between fibroblasts and native human acute myelogenous leukemia (AML) blasts via local cytokine networks results in increased proliferation and decreased apoptosis of AML cells as well as increased levels of proangiogenic Interleukin 8. Leukemia research, 29, 185-96. https://doi.org/10.1016/j.leukres.2004.06.008
  27. Scharnhorst V, van der Eb AJ, Jochemsen AG (2001). WT1 proteins: functions in growth and differentiation. Gene, 273, 141-61. https://doi.org/10.1016/S0378-1119(01)00593-5
  28. Schmid D, Heinze G, Linnerth B, et al (1997). Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia. Leukemia, 11, 639-43. https://doi.org/10.1038/sj.leu.2400620
  29. Shibata M, Nezu T, Kanou H, et al (2002). Decreased production of interleukin-12 and type 2 immune responses are marked in cachectic patients with colorectal and gastric cancer. J Clin Gastroenterol, 34, 416-20. https://doi.org/10.1097/00004836-200204000-00006
  30. Sugiyama H (2010). WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy. Japanese J Clin Oncol, 40, 377-87. https://doi.org/10.1093/jjco/hyp194
  31. Tamaki H, Ogawa H, Ohyashiki K, et al (1999). The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplnstic syndromes. Leukemia, 13, 393-9. https://doi.org/10.1038/sj.leu.2401341
  32. Tugues S, Burkhard S, Ohs I, et al (2014). New insights into IL-12-mediated tumor suppression. Cell Death & Differentiation, 22, 237-46.
  33. Wagner N, Panelos J, Massi D, et al (2008). The Wilms' tumor suppressor WT1 is associated with melanoma proliferation. Pflugers Archiv-European J Physiol, 455, 839-47. https://doi.org/10.1007/s00424-007-0340-1
  34. Xu M, Mizoguchi I, Morishima N, et al (2010). Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. Clinical and Developmental immunology, 832454, 9.
  35. Yamamoto S, Tsuda H, Kita T, et al (2007). Clinicopathological significance of WT1 expression in ovarian cancer: a possible accelerator of tumor progression in serous adenocarcinoma. Virchows Archiv, 451, 27-35. https://doi.org/10.1007/s00428-007-0433-4
  36. Yang L, Han Y, Saiz FS, et al (2007). A tumor suppressor and oncogene: the WT1 story. Leukemia, 21, 868-76.
  37. Zand AM, Imani S, Saadati M, et al (2012). Statistical approach to discovery of factors impacting on emergence of blood cancers in Iran. Asian Pac J Cancer Prev, 13, 5965-7. https://doi.org/10.7314/APJCP.2012.13.12.5965

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