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

• Published in: Leukemia Vol. 24; no. 6; pp. 1152 - 1159
• Main Authors: NÜCKEL, H, SWITALA, M, SELLMANN, L, HORN, P. A, DÜRIG, J, DÜHRSEN, U, KÜPPERS, R, GROSSE-WILDE, H, REBMANN, V
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing Group 01.06.2010
• Subjects: Biological and medical sciences; Biological markers; Case-Control Studies; Chronic lymphocytic leukemia; Development and progression; Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; GPI-Linked Proteins; Health risks; Hematologic and hematopoietic diseases; Histocompatibility Antigens Class I - blood; Humans; Intercellular Signaling Peptides and Proteins - blood; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Ligands; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Major histocompatibility complex; Male; Medical sciences; Membrane proteins; Membranes; Middle Aged; Multivariate analysis; Natural killer cells; NKG2 antigen; Patient outcomes; Patients; Peripheral blood; Physiological aspects; Receptors; Retrospective Studies; Risk assessment; Thawing; Tumor cells; ZAP-70 protein; Germany; CLL; Prognosis; Hematology; Ligand; NKG2D receptor; Biological marker; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Soluble form; Chronic lymphocytic leukemia; prognostic marker; NKG2D ligands; Lymphoproliferative syndrome; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2010.74

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.