title: CTLA-4 affects expression of key cell cycle regulators of G0/G1 phase in neoplastic lymphocytes from patients with chronic lymphocytic leukaemia.
abstract: Previously, we showed that cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is overexpressed in chronic lymphocytic leukaemia (CLL) and its expression is correlated with the expression of the major regulators of G1 phase progression: cyclins D2 and D3, and cyclin-dependent kinase inhibitory protein 1 (p27 (KIP1) ). In the present study, we blocked CTLA-4 on the surface of both CLL cells and normal B lymphocytes to investigate the impact of CTLA-4 on the expression of the mentioned G1 phase regulators. We found that in CLL patients and in healthy individuals, the median proportions of cyclin D2-positive cells as well as cyclin D3(+) cells significantly decreased following CTLA-4 blockade. Moreover, CTLA-4 blockade led to an increase in the median frequencies of p27 (KIP1) -positive cells, although this increase was marked only in CLL patients. Our study showed that CTLA-4 affects the expression of the key regulators of G1 phase progression in CLL cells as well as in normal B lymphocytes and may contribute to a better understanding of the role of CTLA-4 in the regulation of G1 phase progression.
authors.affiliation: Laboratory of Immunopathology, Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wrocław, Poland. ciszak@iitd.pan.wroc.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ciszak
authors.affiliation: Laboratory of Immunopathology, Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
authors.affiliation: Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, L. Pasteura 4, 50-367, Wrocław, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wolowiec
authors.affiliation: Laboratory of Immunopathology, Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szteblich
authors.affiliation: Laboratory of Immunopathology, Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wrocław, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Kosmaczewska
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C583905:SLC44A4 protein, human
keywords: CTLA-4 (CD152); Chronic lymphocytic leukaemia (CLL); Cyclin D2; Cyclin D3; p27 KIP1