Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia.
OBJECTIVE
p53 status and CD38 antigen are biological factors influencing response to therapy and clinical course in B-cell chronic lymphocytic leukemia (B-CLL). This study tests the hypothesis that soluble p53 alone and in association with CD38 can enucleate B-CLL subsets at worse prognosis.


METHODS
Wild and mutant forms of p53 protein were evaluated in 197 B-CLL patients at diagnosis or before progression by an immunoenzymatic method in plasma using an anti-p53 monoclonal antibody. CD38 expression was analyzed by a multicolor flow cytometric assay.


RESULTS
Higher levels of both soluble p53 (sp53) and CD38 were significantly correlated with intermediate and high Rai stages, with higher beta2-microglobulin and soluble CD23 values, determined at diagnosis. Shorter overall survival (OS) and progression-free survival (PFS) were both observed in sp53+ and CD38+ patients (p<0.0001). Simultaneous positivity or negativity for sp53 and CD38 identified two subsets of patients, the former with a worse prognosis and the latter with a better prognosis with regard to PFS (p<0.0001) and OS (p<0.0001). The predictive value of sp53 and CD38 was retained among the patients within the intermediate Rai risk group.


CONCLUSIONS
sp53 and CD38 together with ZAP-70 were confirmed to be independent prognostic factors in multivariate analysis. With regard to PFS, ZAP-70, sp53 and CD38 were confirmed to be independent prognostic factors. Concerning OS, ZAP-70, CD38 and age (< or > 60 years) were independent prognostic factors whereas sp53 showed only a tendency towards statistical significance.
Del Principe
Maria Ilaria
MI
Department of Hematology, Università Tor Vergata, Ospedale S.Eugenio, Rome, Italy.
Del Poeta
Giovanni
G
Venditti
Adriano
A
Buccisano
Francesco
F
Maurillo
Luca
L
Marini
Rita
R
Cox
Maria Christina
MC
Panetta
Paola
P
Suppo
Giovanna
G
Degan
Massimo
M
Bruno
Antonio
A
Gattei
Valter
V
Amadori
Sergio
S
D051997:ADP-ribosyl Cyclase 1 / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002051:Burkitt Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012995:Solubility; D016159:Tumor Suppressor Protein p53 / Q000097:blood*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1; D014740:Vidarabine; C024352:fludarabine