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Increased expression of vascular endothelial growth factor (VEGF) in bone marrow of patients with myeloproliferative disorders (MPD)

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Pathology Oncology Research

Abstract

Angiogenesis is a multistep process of the development of capillaries from established blood vessels. Angiogenesis probably plays a significant role in the development and progression of hematopoietic malignancies. Higher microvascular density and increased serum levels of proangiogenic factors such as vascular endothelial growth factor (VEGF) or basic fibroblasts growth factor (bFGF) have been reported in acute and chronic leukemias, myeloproliferative and myelodysplastic disorders, multiple myeloma and lymphomas. The microvessel density of bone marrow stroma in myeloproliferative disorders is increased and VEGF is considered as the most potent endothelial cell activator. The purpose of this study was to examine the expression of VEGF in bone marrow of patients with MPD. 60 paraffin-embedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated. In addition 10 bone marrow core biopsy specimens from adult patients without evidence of malignancy were used as controls. Bone marrow sections were stained immunohistochemically for VEGF (PharMingen, USA). Obtained data show that MPD are associated with an increased expression of VEGF in the bone marrow. This observation support previous studies suggesting that angiogenesis may play a role in the pathophysiology of myeloproliferative disorders. Clinical significance of this phenomenon needs further investigation however thus provides rationale for use of angiogenesis inhibitors in MPD therapy.

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References

  1. Belgore FM, Lip G, Bareford D, et al: Plasma levels of vascular endothelial growth factor (VEGF) in haematological cancers. Br J Haematol 110: 496–497, 2000.

    PubMed  CAS  Google Scholar 

  2. Elliot MA, Mesa RA, Li CY, et al: Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol 117: 288–296, 2002.

    Article  Google Scholar 

  3. Faderl S, Talpaz M, Estrov Z, et al: The biology of chronic myeloid leukemia. N Engl J Med 341: 164–172, 1999.

    Article  PubMed  CAS  Google Scholar 

  4. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31, 1995.

    Article  PubMed  CAS  Google Scholar 

  5. Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29: 577–582, 1981.

    PubMed  CAS  Google Scholar 

  6. Janowska-Wieczorek A, Majka M, Marquez-Curtis L, et al: Bcr-abl-positive cells secrete angiogenic factors including matrix metalloproteinases and stimulate angiogenesis in vivo in Martigel implants. Leukemia 16: 1160–1166, 2002.

    Article  PubMed  CAS  Google Scholar 

  7. Li CY: The role of morphology, cytochemistry and immunochemistry in the diagnosis of chronic myeloproliferative diseases. Int J Haematol 76, (Suppl II): 6–8, 2002.

    Article  Google Scholar 

  8. Lundberg LG, Lerner R, Sundelin P, et al: Bone marrow in polycythemia vera, chronic myeloid leukemia and myelofibrosis has an increased vascularity. Am J Pathol 157: 15–19, 2000.

    PubMed  CAS  Google Scholar 

  9. McMahon G: VEGF receptor signaling in tumor angiogenesis. Oncologist 5: 3–10, 2000.

    Article  PubMed  CAS  Google Scholar 

  10. Molica S, Santoro R, Iuliano F, et al: Serum levels of vascular endothelial growth factor in chronic leukemias. A comparative study with emphasis on myeloproliferative disorders. Hematologica 86:771, 2001.

    CAS  Google Scholar 

  11. Murphy S, Peterson P, Hand H, et al: Experience of the Polycytaemia Vera Study Group with essential thrombocytaemia: A final report on diagnostic criteria, survival and leukemic transition by treatment. Semin Hematol 34: 29–35, 1997.

    PubMed  CAS  Google Scholar 

  12. Musolino C, Calabro L, Bellomo G, et al: Soluble angiogenic factors: implications for chronic myeloproliferative disorders. Am J Hemat 69: 159–163, 2002.

    Article  PubMed  CAS  Google Scholar 

  13. Pearson TC, Messinezy M: The diagnostic criteria of polycythemia rubra vera. Leuk Lymphoma 22, (suppl1): 87–94, 1996.

    PubMed  Google Scholar 

  14. Perez-Atayde AR, Sallan SE, Tedrow U, et al: Spectrum of tumor angiogenesis in bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 150: 815–821, 1997.

    PubMed  CAS  Google Scholar 

  15. Di Raimondo F, Palumbo G, Molica S, et al: Angiogenesis in chronic myeloproliferative diseases. Acta Haematol 106: 177–183, 2001.

    Article  PubMed  Google Scholar 

  16. Remmele W, Stenger HE: Vorschlag zur einheitlichen Definition eines Immunreaktiven Score (IRS) fuer den immunohistochemischen Oestrogenrezeptor Nachweis (ER-ICA) im Mammakarzinomgewebe. Pathologe 8: 138–140, 1987.

    PubMed  CAS  Google Scholar 

  17. Shi SR, Key ME, Kalra KL: Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microvave oven heating of tissue sections. J Histochem Cytochem 39: 741–746, 1991.

    PubMed  CAS  Google Scholar 

  18. Tefferi A: The Philadelphia chromosome negative chronic myeloproliferative disorders: A practical overview. Mayo Clin Proc 73: 1177–1184, 1998.

    Article  PubMed  CAS  Google Scholar 

  19. Thomas DA, Giles FJ, Cortes J, et al: Antiangiogenic therapy in leukemia. Acta Haematol 106: 190–207, 2001.

    Article  PubMed  CAS  Google Scholar 

  20. Wróbel T, Mazur G, Surowiak P, et al: Increased expression of vascular endothelial growth factor (VEGF) in bone marrow of multiple myeloma (MM) patients. Eur J Internal Med 14: 98–100, 2003.

    Article  CAS  Google Scholar 

  21. Verstovsek S, Kantarijan H, Manshourti T, et al: Prognostic significance of cellular vascular endothelial growth factor expression in chronic phase chronic myeloid leukemia. Blood 99: 2265–2267, 2002.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Tomasz Wróbel.

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Wróbel, T., Mazur, G., Surowiak, P. et al. Increased expression of vascular endothelial growth factor (VEGF) in bone marrow of patients with myeloproliferative disorders (MPD). Pathol. Oncol. Res. 9, 170–173 (2003). https://doi.org/10.1007/BF03033732

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  • DOI: https://doi.org/10.1007/BF03033732

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