Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity.

Several studies have emphasized the significance of neoangiogenesis for tumor growth and progression, but few have focused on malignant hematological disorders. We studied vascular density and architecture in bone marrow samples of patients with chronic myeloproliferative disease (MPD). Vascular structures were immunostained (for von Willebrand factor/FVIII-RAG, CD 31/PECAM or Ulex europeus I for vessels and for vascular endothelial growth factor, VEGF) in samples from patients with polycythemia vera (PV) (n = 7), chronic myelocytic leukemia (CML) (n = 9), and myelofibrosis (MF) (n = 6) when diagnosed and were compared with normal bone marrow specimens (n = 9). We observed that the mean (+/- SD) vessel count per high-power microscopy field (HPF) was 5.3 (+/- 2.1) in normal bone marrow, 5.9 (+/- 2.1) in PV, 10.8 (+/- 3.2) in CML, and 14.4 (+/- 5.5) in MF (P < 0.001 for CMP and MF versus controls). Confocal microscopy, including three-dimensional reconstructions of the blood vessel architecture, confirmed this increased vessel density and revealed tortuous vessel architecture and increased branching in the MPD, particularly in CML and MF. Furthermore, the number of VEGF-positive bone marrow cells was increased in CML and, particularly, in MF. Numbers of VEGF-positive cells and vessels per HPF correlated significantly (r = 0.41; P = 0. 037). Thus the myeloproliferative diseases PV, CML, and MF exhibit neoangiogenesis that is related to diagnosis.

[1]  Samuel Hellman,et al.  Important advances in oncology , 1991 .

[2]  J Thiele,et al.  Three-dimensional reconstruction of histologic structures in human bone marrow from serial sections of trephine biopsies. Spatial appearance of sinusoidal vessels in primary (idiopathic) osteomyelofibrosis. , 1994, Analytical and quantitative cytology and histology.

[3]  N. Weidner Intratumor microvessel density as a prognostic factor in cancer. , 1995, The American journal of pathology.

[4]  Joe W. Gray,et al.  The Molecular Basis of Cancer , 1985 .

[5]  D. Ribatti,et al.  Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. , 1999, Blood.

[6]  T. Grogan,et al.  Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. , 1999, Cancer research.

[7]  D. Cheresh Death to a blood vessel, death to a tumor , 1998, Nature Medicine.

[8]  N. Berlin Diagnosis and classification of the polycythemias. , 1975, Seminars in hematology.

[9]  G. Firestein,et al.  Starving the synovium: angiogenesis and inflammation in rheumatoid arthritis. , 1999, The Journal of clinical investigation.

[10]  S. Sallan,et al.  Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. , 1997, The American journal of pathology.

[11]  Thomas Boehm,et al.  Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance , 1997, Nature.