Content area
Full text
Introduction
The p53 tumor suppressor mediates an adequate reaction of cells to stress. It functions mainly as a transcription factor responding to various stress stimuli by controlling expression of its target genes. The p53 protein participates in control of cell cycle, DNA repair, apoptosis, senescence, cell metabolism and maintaining of genome integrity (1,2). Mutations and deletions of the TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas (3,4).
Recently, the revision of the World Health Organization (WHO) classification of lymphoid neoplasms was published reflecting and summarizing new achievements in the field. The increasing impact of cytogenetic and molecular approaches, including next-generation sequencing (NGS), was emphasized as they incessantly bring new insights and deepen understanding of the lymphoma development, and thus improve diagnosis, prognosis and treatment of this disease. The biologically relevant subgrouping of heterogeneous diffuse large B-cell lymphomas (DLBCL) and appropriate recognition and classification of double/triple-hit lymphomas (DHL/THL) belong to the highlighted diagnostic topics among mature B-cell lymphomas (5). Concurrently, the European Expert Group on NGS-based Diagnostics in Lymphomas (EGNL) summarized the gathered data and divided recurrent mutations in specific lymphomas into five categories having: i) immediate impact on therapy; ii) diagnostic impact; iii) prognostic impact; iv) potential clinical impact in the near future; and v) mutations to be considered for research purposes only. Tumor suppressor TP53 ‘gets through’ a few categories depending on the particular diagnosis. The assessment of its status is essential for clinical decision-making in patients with chronic lymphocytic leukemia (CLL). In addition, the prognostic value of the TP53 status was recognized in splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL) and the subgroup of DLBCL concordantly bearing MYC translocation (6).
The role of p53 in lymphoma has been attributed to its ability to induce apoptosis. Stressed lymphocytes are prone to apoptosis and disruption of the p53-dependent apoptosis seems to be essential for the development and progression of lymphoma. However, direct loss of p53 function by mutation of the TP53 gene is not the only way how to accomplish it. The p53 protein level and function itself might be abrogated by several mechanisms. In addition, inactivation of some other proapoptotic genes (e.g. BIM or NOXA) or hyperactivation of antiapoptotic...