title: Increased angiogenesis in primary myelofibrosis: latent transforming growth factor-β as a possible angiogenic factor.
abstract: OBJECTIVE
  The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis.
  
  
  METHODS
  Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus.
  
  
  RESULTS
  The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value<0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r=0.45; p-value<0.0009) and between degree of microvascular density and fibrosis grade (r=0.80; p-value<0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls.
  
  
  CONCLUSIONS
  Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage.
authors.affiliation: Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: cesarcponce@gmail.com.
authors.forename: Cesar Cilento
authors.initials: CC
authors.lastname: Ponce
authors.affiliation: Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes Lopes Ferrari Chauffaille
authors.affiliation: Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Silvia Saiuli Miki
authors.initials: SS
authors.lastname: Ihara
authors.affiliation: Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Maria Regina Regis
authors.initials: MR
authors.lastname: Silva
keywords: Angiogenesis inducing agents; Antigens, CD34; Fibrosis; Primary myelofibrosis; Transforming growth factor beta