Reduced expression of adhesion molecules and cell signaling receptors by chronic lymphocytic leukemia cells with 11q deletion.
Deletions in chromosome bands 11q22-q23 were recently shown to be one of the most frequent chromosome aberrations in B-cell chronic lymphocytic leukemia (B-CLL). Patients suffering from B-CLL with 11q deletion are characterized by extensive lymphadenopathy, rapid disease progression, and short survival times. Phenotypic and functional characteristics of B-CLL cells with 11q deletion that may help to explain the pathophysiology of this entity are yet unknown. In the present study, B-CLL cells with (n = 19) and without (n = 19) 11q deletion were analyzed for their expression of functionally relevant cell surface molecules (n = 57). B-CLL cells with 11q deletion carried significantly lower levels of the adhesion molecules CD11a/CD18 (integrin alphaL/beta2), CD11c/CD18 (integrin alphaX/beta2), CD31 (PECAM-1), CD48, and CD58 (LFA-3). Furthermore, B-CLL cells with 11q deletion expressed less the cell signaling receptors CD45 (leukocyte common antigen [LCA]), CD6, CD35 (complement receptor 1), and CD39. Reduced CD45 levels and low-level expression of CD49d correlated with decreased overall survival. B-CLL cells with or without 11q deletion did not differ in their growth fractions, expression levels of transcription factor NF-kappaB, or their response to mitogenic stimuli. Decreased levels of functionally relevant adhesion molecules and of cell signaling receptors may contribute to the pathogenesis of the subgroup of B-CLL characterized by 11q22-q23 deletion.
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Medizinische Klinik, mit Schwerpunkt Hämatologie und Onkologie, Charité, Campus Virchow-Klinikum, Humboldt Universität, Berlin, Germany.
Pahl
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Stilgenbauer
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Döhner
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Schriever
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D000251:Adenosine Triphosphatases; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001081:Apyrase; D018845:CD11 Antigens / Q000032:analysis; D018821:CD18 Antigens / Q000032:analysis; D000071178:CD48 Antigen; D018968:CD58 Antigens / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002880:Chromosomes, Human, Pair 11; D017353:Gene Deletion; D006801:Humans; D039441:Integrin alpha4; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D017493:Leukocyte Common Antigens / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D017463:Receptors, Complement 3b / Q000032:analysis; D015398:Signal Transduction / Q000235:genetics*; D015996:Survival Rate
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018821:CD18 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; C062279:CD6 antigen; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017463:Receptors, Complement 3b; D039441:Integrin alpha4; D017493:Leukocyte Common Antigens; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen