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

• DOI: 10.1046/j.1365-2141.2001.02722.x
• Publication Date: 2002-07-26T10:27:39Z
• Authors: Eveline S. J. M. ...; Stefano Rosati; Susan Jacobs; Willem A. Kamps; Edo Vellenga
• Keywords: EXPRESSION; Adult; 0301 basic medicine; CELL GROWTH; FACTOR VEGF; Enzyme-Linked Immunosorbent Assay; RECEPTOR TYROSINE KINASE; Endothelial Growth Factors; TUMOR ANGIOGENESIS; angiogenesis; 03 medical and health sciences; Bone Marrow; Cell Movement; INCREASED ANGIOGENESIS; Humans; acute myeloid leukaemia; RNA, Messenger; Aged; Lymphokines; Neovascularization, Pathologic; ACUTE MYELOBLASTIC-LEUKEMIA; Bone Marrow Examination; MESSENGER-RNA LEVELS; IN-VITRO; Middle Aged; VEGF; Immunohistochemistry; ANG2; bFGF; Leukemia, Myeloid; Case-Control Studies; Culture Media, Conditioned; Acute Disease; Biological Assay; Endothelium, Vascular; FACTOR FAMILY; Cell Division

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.