Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors

Leukemia. 2009 Jan;23(1):162-9. doi: 10.1038/leu.2008.255. Epub 2008 Sep 18.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents / blood*
  • Bone Marrow / blood supply*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / pathology*
  • Humans
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Male
  • Microvessels / growth & development*
  • Middle Aged
  • Neovascularization, Pathologic
  • Prospective Studies
  • RNA, Messenger / blood
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inducing Agents
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A