Haematologica · 2004
Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia.
СтатьяПоддержка исследования: вне правительства СШАВалидационное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Del Principe Maria Ilaria, Del Poeta Giovanni, Venditti Adriano, Buccisano Francesco, Maurillo Luca, Marini Rita, Cox Maria Christina, Panetta Paola, Suppo Giovanna, Degan Massimo, Bruno Antonio, Gattei Valter, Amadori Sergio
Аннотация
BACKGROUND AND OBJECTIVES: 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.
DESIGN AND 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.
INTERPRETATION AND 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.
DESIGN AND 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.
INTERPRETATION AND 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.
Предметные рубрики MeSH
ADP-ribosyl Cyclase 1AdultAgedAged, 80 and overAntimetabolites, AntineoplasticBiomarkers, TumorBurkitt LymphomaDisease ProgressionEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGene Rearrangement, B-Lymphocyte, Heavy ChainHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionImmunophenotypingIn Situ Hybridization, FluorescenceInterphaseLife TablesMaleMiddle AgedNeoplasm ProteinsPredictive Value of TestsPrognosisProportional Hazards ModelsSolubilityTumor Suppressor Protein p53VidarabineZAP-70 Protein-Tyrosine Kinase