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WT1 Overexpression Affecting Clinical Outcome in Non-Hodgkin Lymphomas and Adult Acute Lymphoblastic Leukemia

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Pathology & Oncology Research

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Abstract

The Wilms tumor 1 (WT1) gene has a complex role as a transcriptional regulator, acting as tumor suppressor or oncogene in different malignancies. The prognostic role of its overexpression has been well-studied in leukemias, especially acute myeloid leukemia (AML), but not in lymphomas. For the first time to our knowledge, we present a study demonstrating the correlation of WT1 expression and survival in various non-Hodgkin lymphomas. We also studied the prognostic implications of WT1 overexpression in adult acute lymphoblastic leukemia (ALL). In our sample of 53 patients—25 with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), 9 with peripheral T-cell lymphoma (PTCL), 2 with Burkitt’s lymphoma, 2 with mucosa-associated lymphoid tissue (MALT) lymphoma, and 7 with B-cell ALL—, we measured WT1 mRNA from blood samples by quantitative RT-PCR, and divided the patients into subgroups based on the level of expression. Kaplan–Meier survival curves were drawn and compared using the logrank test. In the sample of DLBCL patients, the difference in overall and disease-free survival between WT1-positive and negative subgroups was significant (p = 0.0475 and p = 0.0004, respectively), and in a few observed cases, a sudden increase in WT1 expression signified a relapse soon followed by death. Disease-free survival curves in MCL and ALL were similarly suggestive of a potential role played by WT1. In PTCL, though WT1-positivity was detected in 4 out of 9 cases, it did not seem to affect survival. The few cases of MALT and Burkitt’s lymphoma all proved to be WT1-negative.

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References

  1. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60(3):509–520

    Article  CAS  PubMed  Google Scholar 

  2. Hohenstein P, Hastie ND (2006) The many facets of the Wilms’ tumour gene, WT1. Hum Mol Genet 15:R196–R201

    Article  CAS  PubMed  Google Scholar 

  3. Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE (1991) Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A 88(21):9618–9622

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Dallosso AR, Hancock AL, Brown KW, Williams AC, Jackson S, Malik K (2004) Genomic imprinting at the WT1 gene involves a novel coding transcript (AWT1) that shows deregulation in Wilms’ tumours. Hum Mol Genet 13:405–415

    Article  CAS  PubMed  Google Scholar 

  5. Hastie ND (2001) Life, sex, and WT1 isoforms – three amino acids can make all the difference. Cell 106:391–394

    Article  CAS  PubMed  Google Scholar 

  6. Morrison AA, Viney RL, Ladomery MR (2008) The post-transcriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta 1785:55–62

    CAS  PubMed  Google Scholar 

  7. Miwa H, Beran M, Aunders GF (1992) Expression of the Wilms tumor gene (WT1) in human leukemias. Leukemia 6:405–409

    CAS  PubMed  Google Scholar 

  8. Bergmann L, Miething C, Maurer U, Brieger J, Karakas T, Weidmann E, Hoelzer D (1997) High levels of Wilms’ tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood 90:1217–1225

    CAS  PubMed  Google Scholar 

  9. Glienke W, Maute L, Koehl U, Esser R, Milz E, Bergmann L (2007) Effective treatment of leukemic cell lines with wt1 siRNA. Leukemia 21:2164–2170

    Article  CAS  PubMed  Google Scholar 

  10. Candoni A, Toffoletti E, Gallina R, Simeone E, Chiozzotto M, Volpetti S, Fanin R (2011) Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant 25(2):308–316

    Article  CAS  PubMed  Google Scholar 

  11. Nowakowska-Kopera A, Sacha T, Florek I, Zawada M, Czekalska S, Skotnicki AB (2009) Wilms’ tumor gene 1 expression analysis by real-time quantitative polymerase chain reaction for monitoring of minimal residual disease in acute leukemia. Leuk Lymphoma 50(8):1326–1332

    Article  CAS  PubMed  Google Scholar 

  12. Boublikova L, Kalinova M, Ryan J, Quinn F, O’Marcaigh A, Smith O, Browne P, Stary J, McCann SR, Trka J, Lawler M (2006) Wilms’ tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring. Leukemia 20(2):254–263

    Article  CAS  PubMed  Google Scholar 

  13. Busse A, Gökbuget N, Siehl JM, Hoelzer D, Schwartz S, Rietz A, Thiel E, Keilholz U (2009) Wilms’ tumor gene 1 (WT1) expression in subtypes of acute lymphoblastic leukemia (ALL) of adults and impact on clinical outcome. Ann Hematol 88(12):1199–1205

    Article  CAS  PubMed  Google Scholar 

  14. Sadek HA, El-Metnawey WH, Shaheen IA, Korshied MM, Mohamed AS (2011) Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts in Egyptian acute lymphoblastic leukemia patients. J Investig Med 59(8):1258–1262

    CAS  PubMed  Google Scholar 

  15. Drakos E, Rassidakis GZ, Tsioli P, Lai R, Jones D, Medeiros LJ (2005) Differential expression of WT1 gene product in non-Hodgkin lymphomas. Appl Immunohistochem Mol Morphol 13:132–137

    Article  CAS  PubMed  Google Scholar 

  16. Mazrouei S, Ziaei A, Tanhaee AP, Keyhanian K, Esmaeili M, Baradaran A, Salehi M (2012) Apoptosis inhibition or inflammation: the role of NAIP protein expression in Hodgkin and non-Hodgkin lymphomas compared to non-neoplastic lymph node. J Inflamm Lond 9:4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Hoelzer D, Thiel E, Löffler H, Bodenstein H, Plaumann L, Büchner T, Urbanitz D, Koch P, Heimpel H, Engelhardt R (1983) Recruiting patients and results of a preliminary study on the therapy of acute lymphatic leukemia and acute undifferentiated leukemia in adults. Onkologie 6(4):170–174

    Article  CAS  PubMed  Google Scholar 

  18. Wang YF, Yang YL, Gao ZF, Zhou CJ, Gregg X, Shi YF, Wang J, Yang XF, Ke XY (2012) Clinical and laboratory characteristics of systemic anaplastic large cell lymphoma in Chinese patients. J Hematol Oncol 5:38

    Article  PubMed Central  PubMed  Google Scholar 

  19. Vadasz Z, Shasha-Lavsky H, Nov Y, Bejar J, Lurie M, Tadmor T, Attias D (2012) Wilms’ tumor gene 1: a possible new proangiogenic factor in hodgkin lymphoma. Appl Immunohistochem Mol Morphol. doi:10.1097/PAI.0b013e318259852a

    Google Scholar 

  20. Gurbuxani S (2007) WT1 expression in myelodysplastic syndrome. Leuk Lymphoma 48(3):456–457

    Article  PubMed  Google Scholar 

  21. Perotti D, Mondini P, Giardini R, Ferrari A, Massimino M, Gambirasio F, Pierotti MA, Fossati-Bellani F, Radice P (1998) No evidence of WT1 involvement in a Burkitt’s lymphoma in a patient with Denys-Drash syndrome. Ann Oncol 9(6):627–631

    Article  CAS  PubMed  Google Scholar 

  22. Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RG, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JPP, Ferrando AA (2009) WT1 mutations in T-ALL. Blood 114(5):1038–1045

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Heesch S, Goekbuget N, Stroux A, Tanchez JO, Schlee C, Burmeister T, Schwartz S, Blau O, Keilholz U, Busse A, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (2010) Prognostic implications of mutations and expression of the Wilms tumor 1 (WT1) gene in adult acute T-lymphoblastic leukemia. Haematologica 95(6):942–949

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Oka Y, Tsuboi A, Oji Y, Kawase I, Sugiyama H (2008) WT1 peptide vaccine for the treatment of cancer. Curr Opin Immunol 20(2):211–220

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Social Renewal Operational Programme of Hungary.

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Authors and Affiliations

  1. Institute of Internal Medicine, Division of Haematology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary

    Zsófia Ujj, Miklós Udvardy & László Rejtő

  2. Department of Human Genetics, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary

    Gergely Buglyó, György Vargha & Sándor Biró

Authors
  1. Zsófia Ujj
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  2. Gergely Buglyó
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  3. Miklós Udvardy
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  4. György Vargha
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  5. Sándor Biró
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  6. László Rejtő
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Correspondence to Gergely Buglyó.

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Zsófia Ujj and Gergely Buglyó contributed equally to this work.

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Ujj, Z., Buglyó, G., Udvardy, M. et al. WT1 Overexpression Affecting Clinical Outcome in Non-Hodgkin Lymphomas and Adult Acute Lymphoblastic Leukemia. Pathol. Oncol. Res. 20, 565–570 (2014). https://doi.org/10.1007/s12253-013-9729-7

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  • DOI: https://doi.org/10.1007/s12253-013-9729-7

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