Angiogenesis and vascular endothelial growth factor-/receptor expression in myeloproliferative neoplasms: correlation with clinical parameters and JAK2-V617F mutational status

Br J Haematol. 2009 Jul;146(2):150-7. doi: 10.1111/j.1365-2141.2009.07726.x. Epub 2009 May 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / blood supply
  • Case-Control Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Janus Kinase 2 / genetics*
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Mutation*
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor
  • JAK2 protein, human
  • Janus Kinase 2