Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Dec;81(8):1398–1401. doi: 10.1038/sj.bjc.6693515

Angiogenesis in myelodysplastic syndromes

G Pruneri 1,#, F Bertolini 4,5,#, D Soligo 2, N Carboni 1, A Cortelezzi 3, P F Ferrucci 4, R Buffa 1, G Lambertenghi-Deliliers 2, F Pezzella 6
PMCID: PMC2362976  PMID: 10604739

Abstract

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 ± 9 vs 6 ± 2 and 10 ± 8 respectively) but lower than AML (30 ± 12) and MPD (40 ± 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P = 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia. © 1999 Cancer Research Campaign

Keywords: myelodysplasia, angiogenesis, leukaemia, VEGF

Full Text

The Full Text of this article is available as a PDF (301.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aceñero M. J., González J. F., Gallego M. G., Ballesteros P. A. Vascular enumeration as a significant prognosticator for invasive breast carcinoma. J Clin Oncol. 1998 May;16(5):1684–1688. doi: 10.1200/JCO.1998.16.5.1684. [DOI] [PubMed] [Google Scholar]
  2. Banks R. E., Forbes M. A., Kinsey S. E., Stanley A., Ingham E., Walters C., Selby P. J. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer. 1998 Mar;77(6):956–964. doi: 10.1038/bjc.1998.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boehm T., Folkman J., Browder T., O'Reilly M. S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 1997 Nov 27;390(6658):404–407. doi: 10.1038/37126. [DOI] [PubMed] [Google Scholar]
  4. Ferrara N., Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4–25. doi: 10.1210/edrv.18.1.0287. [DOI] [PubMed] [Google Scholar]
  5. Fiedler W., Graeven U., Ergün S., Verago S., Kilic N., Stockschläder M., Hossfeld D. K. Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood. 1997 Mar 15;89(6):1870–1875. [PubMed] [Google Scholar]
  6. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  7. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. doi: 10.1093/jnci/82.1.4. [DOI] [PubMed] [Google Scholar]
  8. Foss H. D., Araujo I., Demel G., Klotzbach H., Hummel M., Stein H. Expression of vascular endothelial growth factor in lymphomas and Castleman's disease. J Pathol. 1997 Sep;183(1):44–50. doi: 10.1002/(SICI)1096-9896(199709)183:1<44::AID-PATH1103>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  9. Fukumura D., Xavier R., Sugiura T., Chen Y., Park E. C., Lu N., Selig M., Nielsen G., Taksir T., Jain R. K. Tumor induction of VEGF promoter activity in stromal cells. Cell. 1998 Sep 18;94(6):715–725. doi: 10.1016/s0092-8674(00)81731-6. [DOI] [PubMed] [Google Scholar]
  10. Gimbrone M. A., Jr, Leapman S. B., Cotran R. S., Folkman J. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med. 1972 Aug 1;136(2):261–276. doi: 10.1084/jem.136.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham C. H., Rivers J., Kerbel R. S., Stankiewicz K. S., White W. L. Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant melanomas. Am J Pathol. 1994 Sep;145(3):510–514. [PMC free article] [PubMed] [Google Scholar]
  12. Greenberg P., Cox C., LeBeau M. M., Fenaux P., Morel P., Sanz G., Sanz M., Vallespi T., Hamblin T., Oscier D. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079–2088. [PubMed] [Google Scholar]
  13. Lewis C. E., Leek R., Harris A., McGee J. O. Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol. 1995 May;57(5):747–751. doi: 10.1002/jlb.57.5.747. [DOI] [PubMed] [Google Scholar]
  14. Linderholm B., Tavelin B., Grankvist K., Henriksson R. Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma. J Clin Oncol. 1998 Sep;16(9):3121–3128. doi: 10.1200/JCO.1998.16.9.3121. [DOI] [PubMed] [Google Scholar]
  15. Möhle R., Green D., Moore M. A., Nachman R. L., Rafii S. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):663–668. doi: 10.1073/pnas.94.2.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nguyen M., Watanabe H., Budson A. E., Richie J. P., Hayes D. F., Folkman J. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst. 1994 Mar 2;86(5):356–361. doi: 10.1093/jnci/86.5.356. [DOI] [PubMed] [Google Scholar]
  17. Perez-Atayde A. R., Sallan S. E., Tedrow U., Connors S., Allred E., Folkman J. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol. 1997 Mar;150(3):815–821. [PMC free article] [PubMed] [Google Scholar]
  18. Salven P., Teerenhovi L., Joensuu H. A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin's lymphoma. Blood. 1997 Oct 15;90(8):3167–3172. [PubMed] [Google Scholar]
  19. Vacca A., Ribatti D., Roncali L., Ranieri G., Serio G., Silvestris F., Dammacco F. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol. 1994 Jul;87(3):503–508. doi: 10.1111/j.1365-2141.1994.tb08304.x. [DOI] [PubMed] [Google Scholar]
  20. Weidner N., Semple J. P., Welch W. R., Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1–8. doi: 10.1056/NEJM199101033240101. [DOI] [PubMed] [Google Scholar]
  21. Yamaguchi H., Ishii E., Saito S., Tashiro K., Fujita I., Yoshidomi S., Ohtubo M., Akazawa K., Miyazaki S. Umbilical vein endothelial cells are an important source of c-kit and stem cell factor which regulate the proliferation of haemopoietic progenitor cells. Br J Haematol. 1996 Sep;94(4):606–611. doi: 10.1046/j.1365-2141.1996.d01-1855.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES