Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia

Blood. 2000 Nov 15;96(10):3374-80.


Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / blood supply*
  • Cohort Studies
  • Female
  • Histocytochemistry
  • Humans
  • Male
  • Microcirculation
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic / classification
  • Neovascularization, Pathologic / pathology*
  • Polycythemia Vera / diagnosis
  • Polycythemia Vera / physiopathology
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / physiopathology*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / physiopathology