Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients

Paola Monti, Marta Lionetti, Giuseppa De Luca, Paola Menichini, Anna Grazia Recchia, Serena Matis, Monica Colombo, Sonia Fabris, Andrea Speciale, Marzia Barbieri, Massimo Gentile, Simonetta Zupo, Mariella Dono, Adalberto Ibatici, Antonino Neri, Manlio Ferrarini, Franco Fais, Gilberto Fronza, Giovanna Cutrona, Fortunato Morabito

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic lymphocytic leukaemia (CLL) is characterised by a heterogeneous clinical course. Such heterogeneity is associated with a number of markers, including TP53 gene inactivation. While TP53 gene alterations determine resistance to chemotherapy, it is not clear whether they can influence early disease progression. To clarify this issue, TP53 mutations and deletions of the corresponding locus [del(17p)] were evaluated in 469 cases from the O-CLL1 observational study that recruited a cohort of clinically and molecularly characterised Binet stage A patients. Twenty-four cases harboured somatic TP53 mutations [accompanied by del(17p) in 9 cases], 2 patients had del(17p) only, and 5 patients had TP53 germ-line variants. While del(17p) with or without TP53 mutations was capable of significantly predicting the time to first treatment, a reliable measure of disease progression, TP53 mutations were not. This was true for cases with high or low variant allele frequency. The lack of predictive ability was independent of the functional features of the mutant P53 protein in terms of transactivation and dominant negative potential. TP53 mutations alone were more frequent in patients with mutated IGHV genes, whereas del(17p) was associated with the presence of adverse prognostic factors, including CD38 positivity, unmutated-IGHV gene status, and NOTCH1 mutations.

Original languageEnglish
Article number18427
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

ASJC Scopus subject areas

  • General

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