Regulation of angiogenesis in the bone marrow of myelodysplastic syndromes transforming to overt leukaemia

Tamara Keith, Yuko Araki, Masaki Ohyagi, Maki Hasegawa, Kouhei Yamamoto, Morito Kurata, Yasunori Nakagawa, Kenshi Suzuki, Masanobu Kitagawa

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

To investigate the regulatory mechanisms of angiogenesis in the development of myelodysplastic syndromes (MDS) and its progression to overt leukaemia (OL), bone marrow samples from control, paired samples from MDS patients before and after transformation to OL (MDS → OL) and de novo acute myeloid leukaemia (AML) were analysed. Immunohistochemical staining showed a significant increase of bone marrow microvascular density (MVD) in MDS and de novo AML compared with controls. Surprisingly, in MDS, MVD significantly decreased upon transformation to OL, which was also significantly lower than the MVD of de novo AML. This evidence was strengthened by the pattern of angiogenic mediator gene expression, confirming the importance of various angiogenic mediators including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumour necrosis factor α (TNFα), hepatocyte growth factor (HGF) and the angiopoietin family of mediators (Ang-1 and Ang-2) as well as the receptors for angiogenic mediators, such as VEGF receptor 2 (VEGFR2) and the tyrosine kinase receptor, TIE2. By contrast, the anti-angiogenic mediator, transforming growth factor-β (TGFβ) exhibited significantly higher expression in the bone marrow of MDS → OL, indicating the importance of this cytokine as the suppressive factor of angiogenesis in MDS. These findings indicate that the bone marrow microenvironment in MDS → OL and de novo AML differs remarkably, suggesting the different efficacy of anti-angiogenic therapy between de novo AML and leukaemia secondary to MDS.

Original languageEnglish
Pages (from-to)206-215
Number of pages10
JournalBritish Journal of Haematology
Volume137
Issue number3
DOIs
Publication statusPublished - 2007 May
Externally publishedYes

Keywords

  • Angiogenesis
  • Bone marrow
  • Microvasculature
  • Myelodysplastic syndromes
  • Overt leukaemia

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Regulation of angiogenesis in the bone marrow of myelodysplastic syndromes transforming to overt leukaemia'. Together they form a unique fingerprint.

Cite this