Increased bone marrow vascularization in patients with acute myeloid leukaemia: a possible role for vascular endothelial growth factor

Br J Haematol. 2001 May;113(2):296-304. doi: 10.1046/j.1365-2141.2001.02722.x.

Abstract

The present study demonstrated that the vessel number in bone marrow biopsies from acute myeloid leukaemia (AML) patients (n = 23) was significantly increased at diagnosis compared with normal bone marrow (P = 0.019) and was restored to normal levels after achieving complete remission (P = 0.03). The in vitro angiogenic potential of culture supernatant of AML cells was assessed using endothelial cell (EC) migration and proliferation assays. Increased EC migration and EC proliferation was induced in 7/20 and 19/20 AML supernatents respectively. The degree of in vivo neovascularization did not correlate with the ability of AML cells to stimulate in vitro endothelial cell migration and/or proliferation. This might be in part a result of the heterogeneous pattern of angiogenic factors produced by AML cells. The expression of different angiogenic factors was studied using reverse transcription polymerase chain reaction. Cells from 17/20 AML patients showed wide variation in spontaneous vascular endothelial growth factor (VEGF) expression, 4/19 expressed varied spontaneous blastic fibroblast growth factor mRNA levels and all patient samples showed spontaneous interleukin 8 mRNA expression. All AML samples expressed matrix metalloproteinase (MMP)-2 and/or MMP-9. VEGF mRNA expression correlated well with protein level (P = 0.006). A correlation was found between the degree of VEGF expression and neoangiogenesis (correlation coefficient = 0.448, P = 0.05). These results suggest that malignant cell proliferation, angiogenesis and VEGF expression are linked in AML and might contribute to the growth advantage of the malignant counterpart as a result of the paracrine production of growth factors produced by the surrounding endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biological Assay
  • Bone Marrow / blood supply*
  • Bone Marrow Examination
  • Case-Control Studies
  • Cell Division
  • Cell Movement
  • Culture Media, Conditioned
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Immunohistochemistry
  • Leukemia, Myeloid / metabolism*
  • Leukemia, Myeloid / pathology*
  • Lymphokines / analysis
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Middle Aged
  • Neovascularization, Pathologic*
  • RNA, Messenger / analysis
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Culture Media, Conditioned
  • Endothelial Growth Factors
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors