title: Marrow angiogenesis-associated factors as prognostic biomarkers in patients with acute myelogenous leukaemia.
abstract: Bone marrow (BM) neoangiogenesis plays an important role in acute myelogenous leukaemia (AML), and depends on the interplay of members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families. We determined the marrow levels of seven molecules associated with angiogenesis in 52 AML patients before chemotherapy and 20 healthy controls: VEGF-A, VEGF/PlGF, VEGF-C, VEGF-D, Ang-1, Ang-2, and Tie-2. All the molecules were quantified using enzyme-linked immunosorbent assay (ELISA). Comparing to normal controls, the marrow levels of VEGF/PlGF, Ang-2, and Tie-2 were significantly higher, and those of VEGF-C and Ang-1 were significantly lower in the AML patients (P<0.001). A total of 31 patients were further subjected to survival analysis. Patients with lower Tie-2 (<26 ng ml(-1)) and Ang-2 levels (<4500 pg ml(-1)) displayed a survival advantage (P=0.037 and 0.042, respectively), same as patients with higher VEGF/PlGF (> or =1 pg ml(-1)) and VEGF-D levels (> or =350 pg ml(-1)) (P=0.020 and 0.016, respectively). An angio-index ((Ang-2 x Tie-2)/(VEGF/PlGF x VEGF-D)) was established and multivariate Cox regression analysis revealed that patients with higher angio-index values (> or =50) displayed poor prognosis (hazard ratio 5.91, 95% confidence interval 1.99-17.56; P=0.001). The angio-index is closely associated with the clinical outcome of AML patients and may be valuable in disease prognosis.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No.1 Chang-Te Street, Taipei 10048, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lee
authors.forename: H-F
authors.initials: HF
authors.lastname: Tien
authors.forename: C-Y
authors.initials: CY
authors.lastname: Hu
authors.forename: W-C
authors.initials: WC
authors.lastname: Chou
authors.forename: L-I
authors.initials: LI
authors.lastname: Lin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D042787:Receptor, TIE-2 / Q000378:metabolism; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D042787:Receptor, TIE-2