title: Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows.
abstract: OBJECTIVE
  Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from patients with myelofibrosis differed from that in samples from controls.
  
  
  METHODS
  We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin).
  
  
  RESULTS
  In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (p<0.001) and vessels displayed 5.9-fold larger mean perimeters (p<0.001). MVD was 1.8-fold greater in JAK2 V617F-positive than in negative patients (p=0.026). Moreover, 92+/-11 % of vessels in patients with myelofibrosis were pericyte-coated but only 51+/-20 % of vessels in controls (p<0.001). In the two mouse models of myelofibrosis caused by targeting megakaryocytopoesis, wide, pericyte-coated and morphologically aberrant vessels were detected. MVD was significantly greater in bone marrow and spleen samples from animals with myelofibrosis than in wild-type mice.
  
  
  CONCLUSIONS
  We conclude that angiogenesis is similarly abnormal in human and murine myelofibrosis with intense pericyte coating, presumably related to abnormal megakaryocytopoiesis.
authors.affiliation: Division of Hematology and Center for Inflammation and Hematology Research, Department of Medicine, The Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Zetterberg
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Micheline
authors.initials: M
authors.lastname: Tulliez
authors.forename: Renée
authors.initials: R
authors.lastname: Dickie
authors.forename: Hans
authors.initials: H
authors.lastname: Hasselbalch
authors.forename: Rick
authors.initials: R
authors.lastname: Rogers
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
mesh_terms: D000199:Actins / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000098:blood supply / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D050982:GATA1 Transcription Factor / Q000172:deficiency; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology*; D020286:Pericytes / Q000737:chemistry / Q000473:pathology*; D055728:Primary Myelofibrosis / Q000235:genetics / Q000473:pathology*; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000098:blood supply / Q000473:pathology; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D013926:Thrombopoietin / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D000199:Actins; D015415:Biomarkers; D050982:GATA1 Transcription Factor; D011993:Recombinant Fusion Proteins; D053773:Transforming Growth Factor beta1; D013926:Thrombopoietin