Expression and cellular localization of vascular endothelial growth factor A and its receptors in acute and chronic leukemias: an immunohistochemical study.
We aimed to study the expression of phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR-2), a membrane-bound tyrosine kinase receptor to vascular endothelial growth factor, in 76 cases of leukemia and nonneoplastic myeloproliferative disease and in 8 reactive bone marrows. The microvessel density (MVD) and the expression of both pVEGFR-2 and its ligand, VEGFA, were evaluated in these cases. We used archival cases and immunohistochemistry with a monoclonal antibody generated by us to the autophosphorylation sites in the cytoplasmic tail of VEGFR-2 and von Willebrand factor antibody to evaluate MVD. Our results demonstrate increased expression of this phosphorylated receptor in the neoplastic cells in acute myeloid and lymphoblastic leukemias. This correlated with increased MVD and VEGFA expression by the neoplastic cells. Interestingly, there was nuclear relocation of this receptor in these diseases. This raises the possibility that pVEGFR-2 may be involved in the transcriptional regulation of these leukemias. Small molecule inhibitors to this receptor may therefore be a useful adjunct in the therapy for these diseases.
Zhang
Youyi
Y
Stem Cell Laboratory, National Blood Service, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9BQ, UK. yyzhangumu@yahoo.com
Pillai
Geetha
G
Gatter
Kevin
K
Blázquez
Cristina
C
Turley
Helen
H
Pezzella
Francesco
F
Watt
Suzanne M
SM
D000328:Adult; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D014841:von Willebrand Factor / Q000276:immunology
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2