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

Maria R. Ricciardi, Maria T. Petrucci, Chiara Gregorj, Cristina Ariola, Roberto M. Lemoli, Miram Fogli, Francesca R. Mauro, Raffaella Cerretti, Robin Foà, Franco Mandelli, Agostino Tafuri

Research output: Contribution to journalArticle

Abstract

The role of apoptosis and cell kinetics in the mechanisms of disease progression of chronic lymphocytic leukaemia (CLL) is still unclear. In the present study, we investigated the susceptibility of leukaemic cells taken from 75 CLL patients with either stable (STD) or progressive disease (PRD) to enter apoptosis. Particular attention was paid to the relationship between cell cycle status and autologous serum (AS). The susceptibility to enter apoptosis 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 presence of AS (mean = 23.03% ± 17.9 versus 11.27% ± 7.6; P = 0.01). Furthermore, 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 expression of the negative cell cycle regulator p27 kip1 (P = 0.03). These kinetic 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 from PRD cases are characterized by a higher degree quiescence and much lower susceptibility to apoptosis when compared with STD ones. In this context, AS does not appear to play a specific role. The association between these kinetic characteristics and disease progression in CLL prompts further studies to establish whether higher quiescence may be responsible for the decreased susceptibility of PRD cells to enter apoptosis.

Original languageEnglish
Pages (from-to)391-399
Number of pages9
JournalBritish Journal of Haematology
Volume113
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Cell cycle
  • Chronic lymphocytic leukaemia
  • Disease progression
  • p27

ASJC Scopus subject areas

  • Hematology

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    Ricciardi, M. R., Petrucci, M. T., Gregorj, C., Ariola, C., Lemoli, R. M., Fogli, M., Mauro, F. R., Cerretti, R., Foà, R., Mandelli, F., & Tafuri, A. (2001). Reduced susceptibility to apoptosis correlates with kinetic quiescence in disease progression of chronic lymphocytic leukaemia. British Journal of Haematology, 113(2), 391-399. https://doi.org/10.1046/j.1365-2141.2001.02708.x