We analyzed TP53 mutations in 483 chronic lymphocytic leukemia patients at different phases of the disease and found a higher incidence of mutations at the later phases and a distinctive mutation profile in each phase. p53 function evaluated by immunoblotting and flow cytometry after cell irradiation was impaired in 28/109 cases. Three phenotipycally different dysfunctions were observed: type I, associated with heterozygous missense TP53 mutations - typically present at diagnosis - and partially resistant to radiation-induced killing; type II and III, with a higher incidence of microdeletions, nonsense mutations and bi-allelic TP53 defects - common in progressive and chemoresistant cases - and a complete radioresistance. Furthermore, in 4/28 patients, all chemoresistant, we found p53 dysfunctions without TP53 mutations. In chronic lymphocytic leukemia patients, a disease phase-specific variability in the p53 mutation profile and function takes place, and both analyses could be useful to guide treatment choices.

Identification of molecular and functional patterns of p53 alterations in chronic lymphocytic leukemia patients in different phases of the disease / Marinelli, Marilisa; Peragine, Nadia; Di Maio, V; Chiaretti, Sabina; De Propris, Ms; Raponi, Sara; Tavolaro, Simona; Mauro, Francesca Romana; DEL GIUDICE, Ilaria; Guarini, Anna; Foa, Roberto. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 98:3(2013), pp. 371-375. [10.3324/haematol.2012.069906]

Identification of molecular and functional patterns of p53 alterations in chronic lymphocytic leukemia patients in different phases of the disease.

MARINELLI, MARILISA;PERAGINE, NADIA;Di Maio V;CHIARETTI, sabina;RAPONI, SARA;TAVOLARO, SIMONA;MAURO, Francesca Romana;DEL GIUDICE, ILARIA;GUARINI, Anna;FOA, Roberto
2013

Abstract

We analyzed TP53 mutations in 483 chronic lymphocytic leukemia patients at different phases of the disease and found a higher incidence of mutations at the later phases and a distinctive mutation profile in each phase. p53 function evaluated by immunoblotting and flow cytometry after cell irradiation was impaired in 28/109 cases. Three phenotipycally different dysfunctions were observed: type I, associated with heterozygous missense TP53 mutations - typically present at diagnosis - and partially resistant to radiation-induced killing; type II and III, with a higher incidence of microdeletions, nonsense mutations and bi-allelic TP53 defects - common in progressive and chemoresistant cases - and a complete radioresistance. Furthermore, in 4/28 patients, all chemoresistant, we found p53 dysfunctions without TP53 mutations. In chronic lymphocytic leukemia patients, a disease phase-specific variability in the p53 mutation profile and function takes place, and both analyses could be useful to guide treatment choices.
2013
TP53 MUTATION, POOR-PROGNOSIS, PROGRESSION, ATM, INACTIVATION, DYSFUNCTION, EXPRESSION, SURVIVAL, DELETION, DNA
01 Pubblicazione su rivista::01a Articolo in rivista
Identification of molecular and functional patterns of p53 alterations in chronic lymphocytic leukemia patients in different phases of the disease / Marinelli, Marilisa; Peragine, Nadia; Di Maio, V; Chiaretti, Sabina; De Propris, Ms; Raponi, Sara; Tavolaro, Simona; Mauro, Francesca Romana; DEL GIUDICE, Ilaria; Guarini, Anna; Foa, Roberto. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 98:3(2013), pp. 371-375. [10.3324/haematol.2012.069906]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/485846
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