Chronic lymphocytic leukemia is associated with a highly heterogeneous disease course in terms of clinical outcomes and responses to chemoimmunotherapy. This heterogeneity is partly due to genetic aberrations identified in chronic lymphocytic leukemia cells such as mutations of TP53 and/or deletions in chromosome 17p [del(17p)], resulting in loss of one TP53 allele. These aberrations are associated with markedly decreased survival and predict impaired response to chemoimmunotherapy thus being among the strongest predictive markers guiding treatment decisions in chronic lymphocytic leukemia. Clinical trials demonstrate the importance of accurately testing for TP53 aberrations [both del(17p) and TP53 mutations] before each line of treatment to allow for appropriate treatment decisions that can optimize patients' outcomes. The current report reviews the diagnostic methods to detect TP53 disruption better, the role of TP53 aberrations in treatment decisions and current therapies available for patients with chronic lymphocytic leukemia carrying these abnormalities. The standardization in sequencing technologies for accurate identification of TP53 mutations and the importance of continued evaluation of TP53 aberrations throughout initial and subsequent lines of therapy remain unmet clinical needs as new therapeutic alternatives become available.

Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Hôpital Avicenne AP HP UMR INSERMU978 Paris 13 University Bobigny France

Hospital Clinic of Barcelona University of Barcelona Institute of Biomedical Research August Pi i Sunyer Barcelona and CIBERONC Spain

Internal Medicine 3 Ulm University Germany and Innere Medizin 1 Universitätsklinikum des Saarlandes Homburg Germany

Medical University of Vienna Austria

Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele Milan Italy

University of Oxford UK

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