Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia

Abstract

In chronic lymphocytic leukemia (CLL), inhibition of spontaneous apoptosis determines a worse prognosis and increasing evidences show that disease progression relies also upon cycling CLL cells. We investigated bcl-2, as measure of apoptosis, and CD71, as measure of proliferation, by flow cytometry in 265 patients with CLL. Combining bcl-2 with CD71 values, we defined three subgroups: (1) bcl2 − CD71−; (2) bcl2 + CD71+; and (3) bcl2 + CD71− or bcl2− CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p < 0.00001) and in patients with bcl2 + CD71+ (p < 0.00001 and p = 0.02). The patients with discordant in bcl2 + CD71− and bcl2− CD71+ showed an intermediate outcome. Noteworthy, patients with bcl2 + CD71+ showed a shorter PFS within ZAP-70 negative subgroup (p = 0.00009). In multivariate analysis of PFS, age (p = 0.005), beta-₂ microglobulin (B₂-M) (p = 0.003), bcl-2 (p = 0.004), CD49d (p = 0.001), and ZAP-70 (p < 0.001) resulted to be significant prognostic factors. The independent prognostic significance of B₂-M (p = 0.009) and bcl-2 (p = 0.03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL.

Keywords:

• Bcl-2
• CD71
• ZAP-70
• flow cytometry
• CLL
• prognostic factors

Acknowledgements

This study was supported in part by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST), Programmi di Ricerca di Interesse Nazionale, 2005 and by Ministero della Salute (Ricerca Finalizzata Istituto di Ricovero e Cura a Carattere Scientifico [IRCCS], Rome, Italy. The authors thank the members of our Department of Haematology clinical staff for their invaluable support to our CLL clinical research program.