title: Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.
abstract: 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.
authors.affiliation: Division of Hematology and Internal Medicine, the Division of Hematopathology, and the Cancer Center Statistics Unit, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Mesa
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: G
authors.initials: G
authors.lastname: Schroeder
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000098:blood supply*; D015331:Cohort Studies; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000145:classification / Q000473:pathology*; D011087:Polycythemia Vera / Q000175:diagnosis / Q000503:physiopathology; D055728:Primary Myelofibrosis / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000503:physiopathology