title: Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome.
abstract: We have previously reported that high levels of cellular vascular endothelial growth factor (VEGF) protein correlated with short survival of patients with acute myeloid leukaemia (AML). As VEGF exerts its effects via two receptors, VEGF receptor 1 (VEGFR-1) and VEGFR-2, we evaluated the significance of VEGFR-1 and VEGFR-2 protein levels in AML and myelodysplastic syndrome (MDS), and their relationship to VEGF protein levels. Western blot analysis and radioimmunoassay confirmed and quantified specific protein levels in bone marrow samples from 41 MDS and 66 AML previously untreated patients. VEGFR-1 levels were significantly higher in AML than in MDS (P = 0.0004), but no significant difference was found in the VEGFR-2 levels (P = 0.5). No significant correlation between VEGFRs levels and duration of survival was found. VEGF protein levels were significantly higher in MDS than in AML (P < 0.0001). A Cox proportional-hazard regression model showed increasing VEGF levels to significantly correlate with shorter survival of patients with MDS (P = 0.008), a finding similar to our previous report of the inverse relationship between VEGF levels and survival of AML patients. We found a significant correlation between VEGF and VEGFR-2 levels in both AML and MDS (P < 0.0000001 andP < 0.0002 respectively) but not between VEGF and VEGFR-1 levels. These data suggest that VEGF expression, rather than the expression of its receptors, is the determining factor in the biological behaviour of AML and MDS, and that VEGFRs are differentially expressed in AML and MDS.
authors.affiliation: Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Anna
authors.initials: A
authors.lastname: Rogers
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000032:analysis*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000401:mortality; D008222:Lymphokines / Q000032:analysis*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D015415:Biomarkers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1