title: Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors.
abstract: Antiangiogenic drugs are currently tested in haematological malignancies. As these drugs target different angiogenic regulators, and as cancers are inherently heterogeneous, a detailed characterization of angiogenesis in individual cancers is needed. Hence, we measured bone marrow microvessel density (MVD), plasma concentrations of eight angiogenesis-related parameters and the expression in blood mononuclear cells of 40 angiogenesis-related mRNAs in 93 patients with haematological neoplasias (acute myeloid leukaemia; chronic lymphatic leukaemia; multiple myeloma (MM); or non-Hodgkin's lymphoma (NHL)) before start and after completion of cancer therapy. Compared with healthy individuals, the patients had significantly increased bone marrow MVD, especially patients with advanced stage disease. A novel finding was that patients with NHL also had increased bone marrow MVD. The plasma levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 were significantly increased. VEGF levels were highest in those who did not achieve complete remission after cancer therapy. The mRNA expression of IL-8 was upregulated 15-fold. Our data show that patients with haematological malignancies have increased bone marrow MVD; hence, supporting the notion that bone marrow angiogenesis plays a role in the pathogenesis and progression of these cancers. VEGF, IL-6 and IL-8 seem to contribute to the malignant phenotype.
authors.affiliation: Department of Haematology, Ullevål University Hospital Trust, Oslo, Norway. helene.negaard@medisin.uio.no
authors.forename: H F S
authors.initials: HF
authors.lastname: Negaard
authors.forename: N
authors.initials: N
authors.lastname: Iversen
authors.forename: I M
authors.initials: IM
authors.lastname: Bowitz-Lothe
authors.forename: P M
authors.initials: PM
authors.lastname: Sandset
authors.forename: B
authors.initials: B
authors.lastname: Steinsvik
authors.forename: B
authors.initials: B
authors.lastname: Ostenstad
authors.forename: P O
authors.initials: PO
authors.lastname: Iversen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D001853:Bone Marrow / Q000098:blood supply*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D055806:Microvessels / Q000254:growth & development*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A