Journal
LEUKEMIA & LYMPHOMA
Volume 51, Issue 1, Pages 95-106Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428190903350421
Keywords
Bcl-2; CD71; ZAP-70; flow cytometry; CLL; prognostic factors
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Funding
- Ministero dell'Universita e della Ricerca Scientifica e Tecnologica (MURST)
- Programmi di Ricerca di Interesse Nazionale
- Ministero della Salute (Ricerca Finalizzata Istituto di Ricovero e Cura a Carattere Scientifico [IRCCS], Rome, Italy
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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 (B(2)-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.
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