Increased turnover of nonmalignant T lymphocytes in patients with chronic lymphocytic leukemia may affect clinical...

A unique feature of chronic lymphocytic leukemia (CLL) is the increased number of circulating T cells preventing malignant B cells from undergoing apoptosis. Dysregulated expression of cyclin‑dependent kinase inhibitor 1B (p27Kip1) and cyclin D2 (G1 phase regulators controlling lymphocyte survival) was examined in leukemic B cells but not in nonmalignant T cells.

We aimed to assess antiapoptotic p27Kip1 and cyclin D2 expression in peripheral blood leukemic B and T cells in relation to their ex vivo apoptosis in CLL patients with different clinical course.

Using flow cytometry, we determined the expression of G1 regulators and apoptosis of B and T cells in 47 previously untreated CLL patients (median age 60 [interquartile range, 53-69] years; 26 men) with stable disease (SD) or progressive disease (PD), and 39 controls, matched for age and sex.

We noted increased apoptosis within T cells in the CLL patients as compared with controls (P <0.001), whereas B cells exhibited failed apoptosis. All patients showed higher expression of p27Kip1 and cyclin D2 in the leukemic B and T cells than the controls (P <0.001). A comparative analysis of B and T cells showed pronounced T cell apoptosis in only PD patients (P <0.001). In SD patients, the expression of G1 regulators was higher in T cells than in B cells (P ≤0.02). Increased p27Kip1 expression and low apoptosis within B cells, and lower cyclin D2 expression and high apoptosis within T cells were predictive of earlier disease progression.

CLL progression is associated with increased T‑cell turnover triggered by dysregulated expression of G1 regulators, suggesting the involvement of the nonmalignant T‑cell compartment in the disease pathogenesis and clinical outcomes.