title: Angiogenesis and vascular endothelial growth factor-/receptor expression in myeloproliferative neoplasms: correlation with clinical parameters and JAK2-V617F mutational status.
abstract: Data on angiogenesis in the bone marrow of BCR-ABL1-negative myeloproliferative neoplasm (MPN) patients suggest an increase of the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression, but relations to the JAK2-V617F status remain controversial. We performed immunohistochemical studies of MVD and VEGF-expression in 100 MPN, including 24 essential thrombocythemia- (ET), 46 polycythemia vera- (PV), 26 primary myelofibrosis- (PMF), four myelodysplastic (MDS)/MPN- and 20 control reactive bone marrow cases, and correlated these findings with biological and clinical key data and the JAK2-V617F status. We found significantly increased MVD, particularly that assessed by CD105, and VEGF expression in MPN compared to controls (PMF > PV > MDS/MPN > ET). We observed stronger association between CD105-MVD and VEGF expression, fibrosis, and JAK2-V617F mutant allele burden, compared to CD34-MVD. MVD was strongly increased in MPN with high JAK2-V617F mutant allele burden. Our study highlights the importance of newly formed CD105+ vessels in the bone marrow of MPN patients, and indicates that assessment of CD105-MVD better reflects angiogenic activity in MPN. In addition, it provides evidence that despite the fact that angiogenesis is generally independent of the JAK2-V617F status in MPN, new vessel formation might be linked to Jak2 effects in some cases with high JAK2-V617F mutant allele burden.
authors.affiliation: Department of Hematology, University Hospital Basel, Basel CH-4031, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Medinger
authors.forename: Radek
authors.initials: R
authors.lastname: Skoda
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Alexandre
authors.initials: A
authors.lastname: Theocharides
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D001853:Bone Marrow / Q000098:blood supply; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2