• Agata Kosmaczewska, Lidia Ciszak, Irena Frydecka, Edyta Pawlak, Aleksandra Szteblich, Tomasz Wróbel, and Dariusz Wołowiec.
• Pol. Arch. Med. Wewn. 2025 Feb 14.

IntroductionA 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.ObjectivesAssessment 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 MethodsUsing 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.ResultsWe 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.ConclusionsCLL 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.

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