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Immunology

Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Leukemia volume 24, pages 1607–1616 (2010)Cite this article

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Abstract

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal stem-cell disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Increased apoptosis and suppressed functions of peripheral blood natural killer (NK) cells have been described in MDS patients, but only limited information is available on the phenotypic and functional integrity of NK cells in the bone marrow. In a cohort of 41 patients with distinct clinical subtypes of MDS, we here show that NK cells in the bone marrow show decreased surface expression of the activating receptors DNAM-1 and NKG2D. Notably, decreased receptor expression correlated with elevated bone marrow blast counts and was associated with impaired NK-cell responsiveness to stimulation with the K562 cell line, or co-activation by NKG2D or DNAM-1 in combination with the 2B4 receptor. Furthermore, antibody-masking experiments revealed a central role for DNAM-1 in NK cell-mediated killing of freshly isolated MDS blasts. Thus, given the emerging evidence for NK cell-mediated immune surveillance of neoplastic cells, we speculate that reduced expression of DNAM-1 on bone marrow NK cells may facilitate disease progression in patients with MDS.

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Acknowledgements

We thank all the individuals who voluntarily donated bone marrow for this study. This work was supported by Grants from the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Society, the Swedish Children's Cancer Foundation, the Cancer Society of Stockholm, the Royal Swedish Academy of Sciences, the Tobias Foundation, the Söderberg Foundation, the Belvén Foundation, the Åke Wiberg Foundation, the Karolinska Institutet, the Novartis and the Swiss Foundation for Medical-Biological Stipends.

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  1. M Carlsten and B C Baumann: These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    M Carlsten, B C Baumann, M Simonsson, Y T Bryceson, H-G Ljunggren & K-J Malmberg

  2. Department of Medicine, Center for Experimental Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    M Jädersten, A-M Forsblom, C Hammarstedt, E Hellström-Lindberg & K-J Malmberg

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  1. M Carlsten
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Correspondence to M Carlsten or K-J Malmberg.

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Carlsten, M., Baumann, B., Simonsson, M. et al. Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome. Leukemia 24, 1607–1616 (2010). https://doi.org/10.1038/leu.2010.149

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