title: High acute myeloid leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow.
abstract: BACKGROUND
  Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the relationship between vascular morphology within AML bone marrow biopsies and AML derived VEGFA levels.
  
  
  METHODS
  Vessel count and surface area (Chalkley count) were calculated in AML bone marrow biopsies at diagnosis (n = 32), at remission (n = 8) and Normal Bone Marrow (n = 32) using immunohistochemical staining for FVIII, CD31, CTIV, SMA and VEGFA. VEGFA protein levels were measured.
  
  
  RESULTS
  High vessel count was associated with an immature vessel status. Combining vessel count and Chalkley count different vessel morphology patterns were quantified within AML bone marrow biopsies. Three different subgroups could be distinguished. The subgroup (37.5% of the samples) exhibiting a high vessel count and vessels with predominantly large lumen (normal Chalkley count) was associated with high secreted VEGFA protein levels.
  
  
  CONCLUSIONS
  Different vasculature patterns are seen in AML bone marrow biopsies, defined by combining number and size of vessel. These quantified morphology patterns, combined with VEGFA levels, might be of value in the success of VEGF/VEGFR-signaling interference approaches.
authors.affiliation: Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands.
authors.forename: Alida C
authors.initials: AC
authors.lastname: Weidenaar
authors.forename: Arja
authors.initials: A
authors.lastname: ter Elst
authors.forename: Gineke
authors.initials: G
authors.lastname: Koopmans-Klein
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosati
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.forename: Tiny
authors.initials: T
authors.lastname: Meeuwsen-de Boer
authors.forename: Willem A
authors.initials: WA
authors.lastname: Kamps
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Eveline S J M
authors.initials: ES
authors.lastname: de Bont
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A