Telomere length and cyclin-dependent kinase 1 in patients with chronic lymphocytic leukemia
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Date
2014-08-08
Authors
Schmidt, Robert
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Abstract
The clinical course of patients with Chronic Lymphocytic Leukemia (CLL) is highly
variable, and identifying genetic abnormalities that lead to aggressive disease is of prognostic
and therapeutic importance. Telomere length may be shortened in the CLL cells of some
patients. This is associated with poor prognosis. In addition, cyclin-dependent kinase 1 (CDK1)
mRNA and protein levels may also be increased in CLL. While the traditional role of CDK1 is in
cell cycle control, recent studies have indicated that, along with telomerase, CDK1 plays a key
role in maintaining telomere length. Typically, telomerase is increased in CLL cells with short
telomeres, to prevent further telomere shortening and cell death; however, whether CDK1 is
also required for this activity has been unknown and was the focus of the present study. We
have shown that the CDK1 protein is increased in 52% of CLL patients and particularly in males
(n=62 p<0.02), a subgroup that is known to have a poor prognosis. The protein levels of CDK1
did not correlate with mRNA levels demonstrating that additional factors controlled protein
expression. Importantly, the increase in CDK1 protein did not appear to be related to cell
proliferation, as it did not correlate with CD38, a surrogate marker of cell division. However, the
increase did correlate with the presence of short telomeres (n=16 p<0.05). These results
demonstrate that CDK1 protein expression in CLL is controlled by factors apart from mRNA
expression and that that the increase in CDK1 protein may be a response to telomere
shortening.
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Keywords
kinase 1, chronic lymphocytic leukemia