CTLA-4 overexpression in CD19+/CD5+ cells correlates with the level of cell cycle regulators and disease progression in B-CLL patients
A Kosmaczewska, L Ciszak, K Suwalska, D Wolowiec… - Leukemia, 2005 - nature.com
A Kosmaczewska, L Ciszak, K Suwalska, D Wolowiec, I Frydecka
Leukemia, 2005•nature.comThe gradual accumulation of malignant cells in B-CLL is probably due to disturbances in the
balance between programmed cell death and cell proliferation. It has been recently
suggested that inhibitory CTLA-4 (cytotoxic T lymphocyteassociated antigen 4; CD152)
molecule may be involved in the cell cycle machinery; 1, 2 however, the role of CTLA-4 in
cell cycle progression is relatively well understood in T cells only. CTLA-4 seems to prolong
the progression through the G1 phase of the cell cycle by upregulation of cyclin D2 and …
balance between programmed cell death and cell proliferation. It has been recently
suggested that inhibitory CTLA-4 (cytotoxic T lymphocyteassociated antigen 4; CD152)
molecule may be involved in the cell cycle machinery; 1, 2 however, the role of CTLA-4 in
cell cycle progression is relatively well understood in T cells only. CTLA-4 seems to prolong
the progression through the G1 phase of the cell cycle by upregulation of cyclin D2 and …
The gradual accumulation of malignant cells in B-CLL is probably due to disturbances in the balance between programmed cell death and cell proliferation. It has been recently suggested that inhibitory CTLA-4 (cytotoxic T lymphocyteassociated antigen 4; CD152) molecule may be involved in the cell cycle machinery; 1, 2 however, the role of CTLA-4 in cell cycle progression is relatively well understood in T cells only. CTLA-4 seems to prolong the progression through the G1 phase of the cell cycle by upregulation of cyclin D2 and inhibition of cyclin D3, cdk4, and cdk6 production. 1, 2 CTLA-4 also affects the degradation of cyclin-dependent kinase inhibitor p27KIP1 and contributes to its earlier and stronger re-expression during the late stages of T-cell activation. 1, 2 As little is known about CTLA-4 expression/function in normal and neoplastic B cells, we have extended our previous study concerning G1 cell cycle phase regulators in B-CLL cells3 in the context of their association with the expression of CTLA-4. We estimated both the surface and intracellular expression of CTLA-4 molecule in peripheral blood CD19þ/CD5 þ lymphocytes derived from B-CLL patients in relation to the stage of the disease and the cell cycle phase distribution of these lymphocytes. We also investigated the associations between CTLA-4 expression and the levels of cyclin D2, cyclin D3, and p27KIP1 in these cells. Based on the fact that CTLA-4 gene polymorphisms were reported to affect CTLA-4 protein level, 4 the relationships between the levels of CTLA-4 expression in leukemic cells and CTLA-4 gene polymorphisms in B-CLL patients were also examined.
A total of 39 B-CLL patients (in stages 0–IV according to the Rai classification) and 21 age-and sex-matched healthy controls entered the study. The criteria for diagnosis and disease progression have been previously described. 5 Direct surface and intracellular immunofluorescence staining were performed for the evaluation of the expressions of all studied proteins and the distribution of cell cycle phases. Cells were then analyzed
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