Reduced susceptibility to apoptosis correlates with kinetic quiescence in disease progression of chronic lymphocytic leukaemia

The role of apoptosis and cell kinetics in the mechanisms of disease progre ssion of chronic lymphocytic leukaemia (CLL) is still unclear. In the prese nt study, we investigated the susceptibility of leukaemic cells taken from 75 CLL patients with either stable (STD) or progressive disease (PRD) to en ter apoptosis. Particular attention was paid to the relationship between ce ll cycle status and autologous serum (AS). The susceptibility to enter apop tosis was significantly greater in STD than in PRD, both in standard medium (mean = 23.62% +/- 14.7 versus 14.23% +/- 7.2; P = 0.02) and in the presen ce of AS (mean = 23.03% +/- 17.9 versus 11.27% +/- 7.6; P = 0.01). Furtherm ore, cell kinetics studies revealed a higher quiescence in PRD than in STD cases, both in terms of a lower RNA content (P = 0.04) and of higher expres sion of the negative cell cycle regulator p27(kip1) (P = 0.03). These kinet ic differences were confirmed by short-term in vitro culture both in fetal calf serum and in AS. The results of this study indicate that CLL cells fro m PRD cases are characterized by a higher degree quiescence and much lower susceptibility to apoptosis when compared with STD ones. In this context, A S does not appear to play a specific role. The association between these ki netic characteristics and disease progression in CLL prompts further studie s to establish whether higher quiescence may be responsible for the decreas ed susceptibility of PRD cells to enter apoptosis.