title: GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM.
abstract: There is increasing evidence suggesting that both angiogenesis and endothelial injury are involved in GVHD. To study the dynamics of angiogenesis, we examined 26 patients with AML who had undergone allogeneic haematopoietic SCT. All were in CR and had either acute GVHD (aGVHD) or chronic GVHD (cGVHD). We performed immunohistochemical studies of BM microvessel density (MVD) using Abs against vascular-endothelial (VE)-cadherin, CD34 and CD105, and expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2. At the time of diagnosis, the MVD in AML patients was higher than that in the normal controls, and the MVD decreased after induction chemotherapy. Patients with aGVHD had a significantly higher MVD than patients without aGVHD. Conversely, patients with cGVHD did not have a significantly different MVD. In previous aGVHD, we also found more VEGF+ megakaryocytes. XY FISH in sex-mismatched patients showed that the BM blood vessels consisted mainly of recipient endothelial cells. Taken together, these results suggest that new vessel formation and the VEGF/VEGFR system are involved in aGVHD.
authors.affiliation: Department of Medicine and Haematology, University Hospital Basel, Basel, Switzerland. medingerm@uhbs.ch
authors.forename: M
authors.initials: M
authors.lastname: Medinger
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: C
authors.initials: C
authors.lastname: Bucher
authors.forename: J
authors.initials: J
authors.lastname: Halter
authors.forename: S
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: A
authors.initials: A
authors.lastname: Rovo
authors.forename: J
authors.initials: J
authors.lastname: Passweg
authors.forename: A
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor