e-Article
Therapeutic Options for Patients with TP53 Deficient Chronic Lymphocytic Leukemia: Narrative Review
Document Type
Academic Journal
Source
Cancer Management and Research. February 28, 2021, Vol. 13, p1459, 18 p.
Subject
Language
English
ISSN
1179-1322
Abstract
Introduction The World Health Organisation defines chronic lymphocytic leukaemia (CLL) as low-grade lymphoproliferative neoplasm with [greater than or equal to]5x[10.sup.9]/L clonal B-cells in peripheral circulation. (1,2) Small, mature-appearing CD5, CD19, [...]
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, p53 protein, molecular aberrations, drug resistance
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, p53 protein, molecular aberrations, drug resistance