Therapeutic Options for Patients with TP53 Deficient Chronic Lymphocytic Leukemia: Narrative Review

Cancer Manag Res. 2021 Feb 12:13:1459-1476. doi: 10.2147/CMAR.S283903. eCollection 2021.

Abstract

Chronic lymphocytic leukemia (CLL), which is the most common type of leukemia in western countries in adults, is characterized by heterogeneity in clinical course, prognosis and response to the treatment. Although, in recent years a number of factors with probable prognostic value in CLL have been identified (eg NOTCH1, SF3B1 and BIRC-3 mutations, or evaluation of microRNA expression), TP53 aberrations are still the most important single factors of poor prognosis. It was found that approximately 30% of all TP53 defects are mutations lacking 17p13 deletion, whereas sole 17p13 deletion with the absence of TP53 mutation consists of 10% of all TP53 defects. The detection of del(17)(p13) and/or TP53 mutation is not a criterion itself for starting antileukemic therapy, but it is associated with an aggressive course of the disease and poor response to the standard chemoimmunotherapy. Treatment of patients with CLL harbouring TP53-deficiency requires drugs that promote cell death independently of TP53. Novel and smarter therapies revolutionize the treatment of del(17p) and/or aberrant TP53 CLL, but development of alternative therapeutic approaches still remains an issue of critical importance.

Keywords: chronic lymphocytic leukemia; drug resistance; molecular aberrations; p53 protein.

Publication types

  • Review

Grants and funding

This study was funded by the research grant of Medical University of Lublin [DS176 and DS 175].