Wilms' Tumor Gene (WT1) Expression Correlates with Vascular Epithelial Growth Factor (VEGF) in Newly Acute Leukemia Patients Undergoing Chemotherapy

  • Iranparast, Sara (Immunology Department, Ahvaz Jundishapur University of Medical Sciences) ;
  • Assarehzadegan, Mohammad-Ali (Immunology Department, Ahvaz Jundishapur University of Medical Sciences) ;
  • Heike, Yuji (Department of Hematopoietic Stem cell Transplantation, National Cancer Hospital) ;
  • Hossienzadeh, Mehran (Shafa Medical Center, Ahvaz Jundishapur University of Medical Sciences) ;
  • Khodadadi, Ali (Immunology Department, Ahvaz Jundishapur University of Medical Sciences)
  • Published : 2014.11.28


Background: Today, leukemia is one of the biggest problems worldwide. The Wilms' tumor gene (WT1) and the vascular endothelial growth factor (VEGF) gene are highly expressed in patients with various cancers. This study concerned the relationship between expression of WT1 and VEGF in patients with acute leukemia. Materials and Methods: We evaluated expression of WT1 mRNA and VEGF mRNA using real-time quantitative RT-PCR in the peripheral blood (PB) of 8 newly diagnosed AML and 4 newly diagnosed ALL patients, serially monitored for 2 months. A further 12 normal PB samples served as controls. Results: In the patient group, in comparison with the normal ranges, WT1 and VEGF gene expression was increased, the average values for the expression of these two genes being $0.2852{\pm}0.11$ and $0.2029{\pm}0.018$, respectively. While was no significant relevance between the two genes pre-treatment, a positive link between the two genes in 75% of patients with AML was noted during the procedure of chemotherapy, whereas in 75% of patients with ALL an antiparallel association was observed. Conclusions: Leukemia is associated with production of WT1, which may affect the expression of VEGF.


Supported by : Ahvaz Gondi Shapor University


  1. Achen MG, Williams RA, Minekus MP, et al (2001). Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesis. J Pathol, 193, 147-54.<::AID-PATH757>3.0.CO;2-G
  2. Caldon CE, Lee CS, Sutherland RL, Musgrove EA (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
  3. Cash J, Korchnak A, Gorman J, Tandon Y, Fraizer G (2007). VEGF transcription and mRNA stability are altered by WT1 not DDS (R384W) expression in LNCaP cells. Oncol Rep, 17, 1413-9.
  4. Daniela Cilloni, Francesca Messa, Arruga F (2008). Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1transcript levels in peripheral blood samples collected after chemotherapy. Haematologica, 93, 921-4.
  5. Dohi S, Ohno S, Ohno Y, et al (2010). WT1 expression correlates with angiogenesis in endometrial cancer tissue. Anticancer Res, 30, 3187-92.
  6. Gao L (2000). Selective elimination of leukemic CD34 (+) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood, 95, 2198-203.
  7. Gao L (2003). Human cytotoxic T lymphocytes specific for Wilms' tumor antigen- 1 inhibit engraftment of leukemiainitiating stem cells in non-obese diabetic-severe combined immunodeficient recipients. Transplantation, 75, 1429-36.
  8. Gessler M, Poustka A, Cavenee W, et al (1990). Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature, 343, 774-8.
  9. Graham K, Li W, Williams B, Fraizer G (2006). VEGF is differentially expressed in T1- and DDS-LNCaP cells. Gene Expression, 13, 1-14.
  10. Gregory McCarty OA, Loeb DM (2011. december). WT1 Protein directly regulates expression of vascular endothelial growth factor and is a mediator of tumor response to hypoxia. journal of biological chemistry, 286.
  11. Haber DA, Buckler AJ, T G (1990). An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell, 61, 1257-69.
  12. Hanson J, Gorman J, Reese J (2007). Regulation of vascular endothelial growth factor, VEGF, gene promoter by the tumor suppressor, WT1. Front Biosci, 12, 2279-90.
  13. Hashiba T, Izumoto S, Kagawa N, et al (2007). Expression of WT1 protein and correlation with cellular proliferation in glial tumors. Neurol Med Chir, 47, 165-70.
  14. Hayes DF (2005). Prognostic and predictive factors revisited. Breast, 14, 493-9.
  15. Hylander B, Repasky E, Shrikant P, et al (2006). Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol, 101, 12-7.
  16. Inoue K, Ogawa H, Sonoda Y, et al (1997). Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia. Blood, 89, 1405-12
  17. Keilholz U1, Menssen HD, Gaiger A, et al (2005). Wilms' tumor gene 1 (WT1) in human neoplasia. Leukemia, 19, 1318-23.
  18. Kondo S, Asano M, Matsuo K, Ohmori I, Suzuki H (1994). Vascular endothelila growth factor / vascular permeability factor is detectable in the sera of tumor bearing mice and cancer patients. Biochim Acta Biophys, 1221, 211-4.
  19. Korosh E, Mohammad MG, Rashid R (2012). Report of national cancer registration 2010.
  20. Kreidberg JA, Sariola H, Loring JM, et al (1993). WT-1 is required for early kidney development. Cell, 74, 679-91.
  21. Kusumoto S MI, Bessho M, Matsumoto H M S (1999). The importance of WT1 gene expression in the detection of minimal residual disease. A comparison of WT1 AML/MTG8 transcripts. Rinsho Ketsueki, 40, 511-4.
  22. Lee J, Gray A, Yuan J (1996). Vascular endothelial growth factorrelated protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A, 93, 1988-92.
  23. Maglione D, Guerriero V, Vigeltto G, Persico M, Delli-Bovi P (1991). Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA, 88, 9267-71.
  24. Martin SK, To LB, Horvath N, Zannettino ACW (2004). Angiogenesis in multiple myeloma: implications in myeloma therapy. Cancer Rev A Pac, 02, 119-129.
  25. McCarty G, Awad O, DM L (2011). WT1 protein directly regulates expression of vascular endothelial growth factor and is a mediator of tumor response to hypoxia. J Biol Chem, 286, 51.
  26. Meyer M, Clauss M, Lepple-Wienhues A, et al (1999). A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. EMBO J, 18, 363-74.
  27. Miyoshi Y, Ando A, Egawa C, et al (2002). High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients. 8, 1167-71.
  28. Moazam MM, Eisermann K, Fraizer G (2010). Identifying a role for WT1 in pediatric leukemia. J Clin Oncol, 28.
  29. Oji Y, Miyoshi S, Maeda H, et al (2002). Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers. Int J Cancer, 100, 297-303
  30. Oji Y, Ogawa H, Tamaki H, et al (1999). Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res, 90, 194-204.
  31. Oka Y, Tsuboi A, Kawakami M, et al (2006). Development of WT1 peptide cancer vaccine against hematopoietic malignancies and solid cancers. Curr Med Chem, 13, 2345-52.
  32. Olofsson B, Pajusola K, Kaipainen A, et al (1996). Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA, 93, 2576-81
  33. Ozalp S, Yalcin OT, Acikalin M, et al (2003). Microvessel density (MVD) as a prognosticator in endometrial carcinoma. Eur J Gynaecol Oncol, 24, 305-8.
  34. Phipps, Wilma J, Donovan F (2007). Medical-surgical nursing,7 Ed, Lippincott W, Wilkins.
  35. Rini B (2007). Biological aspects and binding strategies of vascular endothelial growth factor in renal cell carcinoma. Clin Cancer Res, 13, 741-6
  36. Scharnhorst V, van der Eb AJ, Jochemsen AG (2001). WT1 proteins: functions in growth anddifferentiation. Gene, 273, 141-61
  37. Sera T, Hiasa Y, Mashiba T, et al (2008). Wilms' tumour 1 gene expression is increased in hepatocellular carcinoma and associated with poor prognosis. Eur J Cancer, 44, 600-8.
  38. Shimizu M, Toki T, Takagi Y, Konishi I, Fujii S (2000). Immunohisto-chemical detection of the Wilms' tumor gene (WT1) in epithelial ovarian tumors. Int J Gynecol Pathol, 19, 158-63.
  39. Sugiyama H (2001). Wilms' tumor gene WT1: its oncogenic function and clinical application. Int J Hematol, 73, 177-87.
  40. Wagner N1, Panelos J, Massi D, Wagner KD (2008). The Wilms' tumor suppressor WT1 is associated with melanoma proliferation. Pflugers Arch, 455, 839-47.
  41. Xue SA (2005). Elimination of human leukemia cells in NOD/SCID mice by WT1- TCR gene-transduced human T cells. Blood, 106, 3062-7.
  42. Yamamoto S, Tsuda H KT, Maekawa K, et al (2007). Clinicopathological significance of WT1 expression in ovarian cancer: a possible accelerator of tumor progression in serous adenocarcinoma. Virchows Arch, 451, 27-35.
  43. Zamora-Avila DE1, Franco-Molina MA, Trejo-Avila LM, et al (2007). RNAi silencing of the WT1 gene inhibits cell proliferation and induces apoptosis in the B16F10 murine melanoma cell line. Melanoma Res, 17, 341-8.
  44. Zand A M, 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
  45. Zapata-Benavides P1, Tuna M, Lopez-Berestein G, Tari AM (2002). Down-regulation of Wilms' tumor 1 protein inhibits breast cancer proliferation. Biochem Biophys Res Commun, 295, 784-90

Cited by

  1. Candida non albicans with a High Amphotericin B Resistance Pattern Causing Candidemia among Cancer Patients vol.15, pp.24, 2015,
  2. Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels vol.16, pp.16, 2015,
  3. Digital gene expression profiling analysis of childhood acute lymphoblastic leukemia vol.13, pp.5, 2016,