CTLA-4 affects expression of key cell cycle regulators of G0/G1 phase in neoplastic lymphocytes from patients with chronic lymphocytic leukaemia

• Published in: Clinical and experimental medicine 2016-08, Vol.16 (3), p.317-332
• Main Authors: Ciszak, Lidia, Frydecka, Irena, Wolowiec, Dariusz, Szteblich, Aleksandra, Kosmaczewska, Agata
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Cell Cycle; Cell Cycle Proteins - metabolism; Chronic illnesses; Female; Gene expression; Gene Expression Regulation; Hematology; Humans; Internal Medicine; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphocytes; Lymphocytes - pathology; Male; Medicine; Medicine & Public Health; Membrane Transport Proteins - metabolism; Middle Aged; Oncology; Original; Original Article; Phase transitions
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-015-0360-7

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.