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MDS

High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis

Leukemia volume 19, pages 580–585 (2005)Cite this article

Abstract

The pathophysiology of the myelodysplastic syndromes (MDS) is incompletely understood. Tumor necrosis factor (TNF)α levels are elevated, particularly in early-stage MDS, and apoptosis in marrow cells is upregulated. Observations in other models have shown a role for insulin-like growth factor binding protein 3 (IGFBP-3) in TNFα-mediated apoptosis. We observed increased levels of IGFBP-3 in the marrow plasma of patients with MDS (P=0.005) and hypothesized that altered IGFBP-3 levels contribute to the dysregulation of hemopoiesis in MDS by affecting proliferation and apoptosis. Western analysis of marrow plasma from MDS patients revealed an increase in the ratio of intact vs fragmented IGFBP-3 in early-stage MDS (relative to controls) that decreased with MDS disease progression, suggesting increased proteolysis with more advanced disease. Thus, these results provide evidence for dysregulation of IGFBP-3 in patients with MDS. While the data are complex, they are consistent with a modulatory effect of IGFBP-3 on hemopoiesis in MDS. Conceivably, understanding these mechanisms may allow for the development of novel therapeutic strategies.

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Acknowledgements

We thank Dr Deborah Banker for providing the ML-1 and KG1a cell lines and Dr Beverly Torok-Storb for providing the HS-5 stroma cell line. We also thank Dr Yansong Gu, Dr Uwe Platzbecker, Dr Jeffrey Schwartz, Dr Martin Benesch, and Cassandra Beckham for helpful discussions. We thank Kathleen Haugk for immunoblot analysis of phosphorylated IGF receptor in ML-1 cells. This work was supported by PHS Grant CA87948 and HL36444 Grant.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    H-M P Wilson, V Lesnikov, J Ward & H J Deeg

  2. Division of Gerontology and Geriatric Medicine GRECC, VAPSHCS and Harborview Medical Center, University of Washington School of Medicine, Seattle, WA, USA

    S R Plymate

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  1. H-M P Wilson
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Correspondence to H-M P Wilson.

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Wilson, HM., Lesnikov, V., Plymate, S. et al. High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis. Leukemia 19, 580–585 (2005). https://doi.org/10.1038/sj.leu.2403672

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