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Chronic Lymphocytic Leukemia

The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia

Abstract

Soluble or membrane-anchored ligands of NKG2D and their receptor have a critical role in the elimination of tumor cells and disease progression. Plasma samples of 98 patients with B-cell chronic lymphocytic leukemia (CLL) were analyzed with specific ELISA systems for soluble major histocompatibility complex class I-related chains (sMICA and sMICB) and UL-16-binding proteins (ULBP1, 2, and 3). The flow cytometric analysis of MICA on CLL cells and natural killer group 2 member D (NKG2D) receptors on NK cells was performed after thawing of frozen peripheral blood lymphocytes of CLL patients (N=51). Levels of sMICA, sMICB, and sULBP2 were significantly increased (P<0.001) compared with 48 controls, whereas sULBP1 3 were not detectable in patients and controls. Levels of sMICA>990 pg/ml (P=0.014), sMICB>200 pg/ml (P=0.0001), and sULBP2>105 pg/ml (P<0.0001) were associated with poor treatment-free survival (TFS). Neither MICA nor NKG2D expression could be related to clinical parameters. In multivariate analysis Binet stage (P=0.002), sULBP2 (P=0.002) and ZAP-70 (P=0.002) were independent predictive factors for TFS. In patients with Binet stage A, sULBP2 levels>105 pg/ml were strongly associated (P=0.0025) with poor TFS. Our data show that soluble but not membrane-anchored NKG2D ligands or receptors are of prognostic significance in CLL. Moreover, sULBP2 seems to be useful to identify early-stage patients with risk of disease progression.

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Acknowledgements

We are indebted to numerous colleagues for generously contributing information on the clinical course and treatment histories of the study patients. We thank Andrea Kopplin for excellent technical assistance. Holger Nückel and Vera Rebmann were supported by the Deutsche José Carreras Leukämie-Stiftung e.V. (R 07/06v) and Holger Nückel also by the Adolf Messer Stiftung.

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Nückel, H., Switala, M., Sellmann, L. et al. The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia. Leukemia 24, 1152–1159 (2010). https://doi.org/10.1038/leu.2010.74

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  • DOI: https://doi.org/10.1038/leu.2010.74

Keywords

  • NKG2D ligands
  • prognostic marker
  • CLL

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