Increased bone marrow vascularization in patients with acute myeloid leukaemia: a possible role for vascular endothelial growth factor.
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.
de Bont
E S
ES
Division of Paediatric Oncology and Haematology, Department of Paediatrics, Beatrix Children's Hospital, Groningen, The Netherlands. e.de.bont@bkk.azg.nl
Rosati
S
S
Jacobs
S
S
Kamps
W A
WA
Vellenga
E
E
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001681:Biological Assay; D001853:Bone Marrow / Q000098:blood supply*; D001856:Bone Marrow Examination; D016022:Case-Control Studies; D002455:Cell Division; D002465:Cell Movement; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors