TY - JOUR
T1 - Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia
AU - Del Poeta, Giovanni
AU - Del Principe, Maria Ilaria
AU - Maurillo, Luca
AU - Rossi, Francesca Maria
AU - Buccisano, Francesco
AU - Ammatuna, Emanuele
AU - Simotti, Cristina
AU - Zucchetto, Antonella
AU - Catalano, Gianfranco
AU - Bulian, Pietro
AU - Bruno, Antonio
AU - Venditti, Adriano
AU - De Fabritiis, Paolo
AU - Gattei, Valter
AU - Amadori, Sergio
PY - 2010/1
Y1 - 2010/1
N2 - 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-CD717; (2) bcl2+CD71+; and (3) bcl2+CD717 - or bcl2-CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p<.00001) and in patients with bcl2+CD71+ (p<.00001 and p=0.02). The patients with discordant in bcl2+CD717 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<.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.
AB - 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-CD717; (2) bcl2+CD71+; and (3) bcl2+CD717 - or bcl2-CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p<.00001) and in patients with bcl2+CD71+ (p<.00001 and p=0.02). The patients with discordant in bcl2+CD717 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<.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.
KW - Bcl-2
KW - CD71
KW - CLL
KW - Flow cytometry
KW - Prognostic factors
KW - ZAP-70
UR - https://www.scopus.com/pages/publications/74949088506
U2 - 10.3109/10428190903350421
DO - 10.3109/10428190903350421
M3 - Article
C2 - 20001236
AN - SCOPUS:74949088506
SN - 1042-8194
VL - 51
SP - 95
EP - 106
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 1
ER -