title: 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 (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.
authors.affiliation: Department of Hematology, University Tor Vergata, Roma, Italy. g.delpoeta@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Emanuele
authors.initials: E
authors.lastname: Ammatuna
authors.forename: Cristina
authors.initials: C
authors.lastname: Simotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Catalano
authors.forename: Pietro
authors.initials: P
authors.lastname: Bulian
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Paolo
authors.initials: P
authors.lastname: De Fabritiis
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: 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*
chemical_list: 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