title: Identification of molecular and functional patterns of p53 alterations in chronic lymphocytic leukemia patients in different phases of the disease.
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 of 109 cases. Three phenotypically different dysfunctions were observed: type I, associated with heterozygous missense TP53 mutations (typically present at diagnosis) and partially resistant to radiation-induced killing; types 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 of 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.
authors.affiliation: Division of Haematology, Department of Cellular Biotechnologies and Haematology, Sapienza University, Rome, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Valeria
authors.initials: V
authors.lastname: Di Maio
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Sara
authors.initials: S
authors.lastname: Raponi
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D005091:Exons; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000528:radiation effects; D009367:Neoplasm Staging; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53