Increased turnover of non-malignant T lymphocytes in patients with chronic lymphocytic leukemia may affect clinical progression.

Abstract

Introduction: 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 p27Kip1 and cyclin D2 (G1 phase regulators controlling lymphocyte survival) was examined in leukemic B cells but not non-malignant T cells.

Objectives: Assessment of anti-apoptotic p27Kip1 and cyclin D2 in peripheral blood (PB) leukemic B and T cells in relation to ex vivo apoptosis in CLL patients with different clinical courses.

Patients and methods: Using flow cytometry, we determined G1 regulators' expression and apoptosis of B and T cells in 47 previously untreated CLL patients (median age 60.0; 26 men) with stable disease (SD), progressive disease (PD), and 39 controls, matched for age and sex.

Results: We noted increased apoptosis within T cells in CLL patients compared to controls (P <0.001), whereas B cells exhibited failed apoptosis. All patients exerted higher p27Kip1 and cyclin D2 expression in leukemic B and T cells compared to controls (P <0.001). Comparative analysis between B and T cells showed pronounced T cell apoptosis in only PD patients (P <0.001). In SD patients, G1 regulators' expression 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.

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