Angiogenesis and the role of bone marrow endothelial cells in haematological malignancies

Histol Histopathol. 2004 Jul;19(3):935-50. doi: 10.14670/HH-19.935.


Increased microvessel density (MVD) has been observed in the bone marrow (BM) of patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the net result of cumulative phases of angiogenesis and angio-regression and is as such not an indicator of the ongoing angiogenesis at the time of biopsy. There is, therefore, a need for additional methods that allow the estimation of ongoing angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin-embedded tissue to determine the endothelial proliferation fraction. The BM endothelial cells, as a component of the BM stroma, have a close interaction with the malignant cells. In MM, for example, they are involved in the specific homing and are a source of paracrine growth factors. Targeting the BM microvessels will not only influence the nutrient and oxygen supply, but will in addition reduce the growth stimuli provided by the EC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antigens, CD34 / analysis
  • Bone Marrow / blood supply
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Bone Marrow / physiopathology*
  • Cell Division
  • Cell Hypoxia
  • Endothelium, Vascular / pathology*
  • Hematologic Neoplasms / pathology*
  • Hematologic Neoplasms / physiopathology*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Microcirculation
  • Multiple Myeloma / blood supply
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / pathology
  • Multiple Myeloma / physiopathology
  • Myeloproliferative Disorders / pathology*
  • Neovascularization, Pathologic*


  • Angiogenesis Inhibitors
  • Antigens, CD34
  • Ki-67 Antigen