In leukemia, TP53 mutations are not frequent but clearly associate with impaired survival and therapy response. Here, we describe the biological and clinical consequences of TP53 dysfunction as well as the methodical aspects of TP53 analysis in chronic lymphocytic leukemia (CLL). In CLL, TP53 defects are routinely analyzed as part of disease prognostication. Deletions of TP53 locus (17p) have been uniformly detected using I-FISH for several years. Since monoallelic mutations have also been shown to have negative prognostic impact, it is recommended to examine both TP53 mutations and deletions. Several methods are used to detect TP53 mutations, and next-generation sequencing (NGS) is becoming a convenient option for routine analysis. Besides this, ultradeep NGS permits the detection of minor clones carrying TP53 mutations, even below 1%. The prognostic impact of minor TP53-defective subclones is currently unknown, nevertheless they unequivocally bear the risk of being selected by therapy. Prospective studies assessing the consequences of carrying such clones are in progress.

Central European Institute of Technology Center of Molecular Medicine and Faculty of Medicine Department of Internal Medicine Hematology and Oncology Masaryk University Brno Czech Republic

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TP53 aberrations in chronic lymphocytic leukemia: an overview of the clinical implications of improved diagnostics

Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status