Spontaneous in vitro apoptosis of de novo chronic lymphocytic leukemia cells correlates with risk of the disease progression

Abstract

Despite significant progress in treatment, chronic lymphocytic leukemia (CLL) still remains an incurable disease. Major advances have been recently made to understand the molecular pathogenesis underlying CLL, but defects in apoptosis are considered to be the most important factors. Although neoplastic cells are resistant to apoptosis in vivo, they show decreased level of spontaneous in vitro apoptosis, with significant differences among CLL patients. This work compares the level of spontaneous CLL cell apoptosis with prognostic factors and clinical course of the disease. In vitro spontaneous apoptosis of peripheral blood lymphocytes was analyzed using Annexin-V assay (confirmed by TUNEL method) in 135 treatment naïve patients with CLL. Levels of apoptosis after 48 h culture in patients with stable disease were found to be significantly higher than in the group with progressive course of the disease (P = 0.015). Moreover, the level of spontaneous apoptosis after 24 and 48 h of incubation correlated inversely with the progression free survival (P = 0.026 and 0.009, respectively). These results suggest that in vitro spontaneous apoptosis of CLL cells may be a simple and cheap prognostic test which is relatively quick to use, and can predict the course of the disease and response to treatment.

Keywords: chronic lymphocytic leukemia; spontaneous apoptosis; survival; treatment.