Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia.
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 B(2)-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.
Del Poeta
Giovanni
G
Department of Hematology, University Tor Vergata, Roma, Italy. g.delpoeta@tin.it
Del Principe
Maria Ilaria
MI
Maurillo
Luca
L
Rossi
Francesca Maria
FM
Buccisano
Francesco
F
Ammatuna
Emanuele
E
Simotti
Cristina
C
Zucchetto
Antonella
A
Catalano
Gianfranco
G
Bulian
Pietro
P
Bruno
Antonio
A
Venditti
Adriano
A
De Fabritiis
Paolo
P
Gattei
Valter
V
Amadori
Sergio
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000096:biosynthesis*; D016896:Treatment Outcome; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis*
D015703:Antigens, CD; C068126:CD71 antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011990:Receptors, Transferrin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human