Telomere length and cyclin-dependent kinase 1 in patients with chronic lymphocytic leukemia

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Schmidt, Robert
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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.
kinase 1, chronic lymphocytic leukemia