title: Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Università Tor Vergata, Ospedale S.Eugenio, Rome, Italy.
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Rita
authors.initials: R
authors.lastname: Marini
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Cox
authors.forename: Paola
authors.initials: P
authors.lastname: Panetta
authors.forename: Giovanna
authors.initials: G
authors.lastname: Suppo
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: 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
chemical_list: 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