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

Leukemia. 2010 Jun;24(6):1152-9. doi: 10.1038/leu.2010.74. Epub 2010 Apr 29.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I / blood*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Retrospective Studies


  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I
  • Intercellular Signaling Peptides and Proteins
  • MHC class I-related chain A
  • MICB antigen
  • ULBP2 protein, human
  • ULBP3 protein, human