Beschreibung:
<jats:title>Summary</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> 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 <jats:italic>in vitro</jats:italic>. 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.</jats:p>