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Expression of cyclin E in resting and activated B‐chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target
Author(s) -
Decker Thomas,
Hipp Susanne,
Hahntow Ines,
Schneller Folker,
Peschel Christian
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.04901.x
Subject(s) - cyclin e , cyclin b , cyclin a , cyclin dependent kinase 2 , cancer research , biology , cyclin d , cyclin a2 , cell cycle , cyclin dependent kinase , cyclin , microbiology and biotechnology , cell , biochemistry
Summary Disease progression in B‐cell chronic lymphocytic leukaemia (B‐CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B‐CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B‐CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin‐dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B‐CLL cells. Cyclin E and cdk2 expression was increased in B‐CLL cells stimulated with a CpG‐oligodeoxynucleotide and interleukin‐2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro . Pharmacological inhibition of cdk2 activity with Roscovitine‐inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B‐CLL.