title: Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia.
abstract: Vascular endothelial growth factor (VEGF) and its cellular receptor VEGFR-2 have been implicated as the main endothelial pathway required for tumor neovascularization. However, the importance of the VEGF/VEGFR-2 system for angiogenesis in hematologic malignancies such as AML remains to be elucidated. In 32 patients with newly diagnosed untreated AML, we observed by immunohistochemical analysis of bone marrow biopsies significantly higher levels of VEGF and VEGFR-2 expression than in 10 control patients (P <0.001). In contrast, VEGFR-1 staining levels in AML patients were in the same range as in the controls. Expression of VEGF and VEGFR-2 was significantly higher in patients with a high degree of microvessel density compared to those with a low degree (VEGF: P =0.024; VEGFR-2: P =0.040) and correlated well with bone marrow microvessel density (r(s)=0.566 and 0.609, respectively; P <0.001). Furthermore, in patients who achieved a complete remission following induction chemotherapy VEGFR-2 staining levels decreased into the normal range. In conclusion, our results provide evidence for increased expression of VEGF/VEGFR-2 of leukemic blasts and correlation with angiogenesis in the bone marrow of AML patients. Thus, VEGF/VEGFR-2 might constitute promising targets for antiangiogenic and antileukemic treatment strategies in AML.
authors.affiliation: Department of Medicine/Hematology and Oncology, University of Muenster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Padró
authors.forename: R
authors.initials: R
authors.lastname: Bieker
authors.forename: S
authors.initials: S
authors.lastname: Ruiz
authors.forename: M
authors.initials: M
authors.lastname: Steins
authors.forename: S
authors.initials: S
authors.lastname: Retzlaff
authors.forename: H
authors.initials: H
authors.lastname: Bürger
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: T
authors.initials: T
authors.lastname: Kessler
authors.forename: F
authors.initials: F
authors.lastname: Herrera
authors.forename: J
authors.initials: J
authors.lastname: Kienast
authors.forename: C
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.forename: R M
authors.initials: RM
authors.lastname: Mesters
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011975:Receptors, Mitogen / Q000096:biosynthesis / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D012074:Remission Induction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor