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MDS and Apoptosis

Expression of FLIPLong and FLIPShort in bone marrow mononuclear and CD34+ cells in patients with myelodysplastic syndrome: correlation with apoptosis

Leukemia volume 17, pages 2460–2466 (2003)Cite this article

Abstract

Several apoptosis-inducing systems, including Fas/Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) and its receptors, are upregulated in myelodysplastic syndrome (MDS). FLIP (FLICE (FAS-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein)) was identified as an inhibitor of FAS and TRAIL signals. Here, we characterized FLIPLong (FLIPL) and FLIPShort (FLIPS) expression in bone marrow mononuclear cells (BMMNCs) and in CD34+ cells of 29 MDS patients, and in 17 normal volunteers. The expression was correlated with apoptotic indices. In CD34+ cells, FLIPL levels were higher among normal individuals than in MDS patients (P=0.04). Among total BMMNC, FLIPL levels also tended to be higher in normal subjects than in MDS patients, although this difference was not significant (P=0.71). FLIPL levels in CD34+ cells were negatively correlated with apoptosis in both normal and MDS marrows (P=0.03). FLIPShort RNA expression was higher in MDS patients than in normal controls in both BMMNC (P=0.03) and CD34+ cells (P=0.08). In contrast to FLIPL, FLIPSt levels were positively correlated with apoptosis. At the protein level FLIP was most readily detectable in patients with high blast counts. The data suggest that FLIPL and FLIPS are differentially regulated, and that the relative levels of both isoforms play a role in the regulation of apoptosis in MDS.

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Acknowledgements

We acknowledge Andrew Berger, Michelle Black, Josh Royall and Mandy Stoeck (Flow Cytometry Laboratory, FHCRC) for help with flow cytometry and Bobbie M Thomasson for assistance with quantitative PCR. We also thank Heather-Marie Wilson and Valdimir Lesnikov for contributing discussions and technical advice, and Bonnie Larson and Helen Crawford for manuscript preparation. This work was supported by National Institutes of Health Grant CA 87948; MB was supported by a fellowship from the Max Kade-Foundation, New York, USA and UP was supported by a grant from the Alexander von Humboldt-Foundation, Germany.

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Authors and Affiliations

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

    M Benesch, U Platzbecker, J Ward, H J Deeg & W Leisenring

  2. University of Washington, Seattle, WA, USA

    H J Deeg & W Leisenring

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  1. M Benesch
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Benesch, M., Platzbecker, U., Ward, J. et al. Expression of FLIPLong and FLIPShort in bone marrow mononuclear and CD34+ cells in patients with myelodysplastic syndrome: correlation with apoptosis. Leukemia 17, 2460–2466 (2003). https://doi.org/10.1038/sj.leu.2403180

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