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

Authors Stefaniuk P, Onyszczuk J, Szymczyk A, Podhorecka M

Received 25 September 2020

Accepted for publication 20 November 2020

Published 12 February 2021 Volume 2021:13 Pages 1459—1476

DOI https://doi.org/10.2147/CMAR.S283903

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Kenan Onel


Paulina Stefaniuk,1 Julia Onyszczuk,2 Agnieszka Szymczyk,3 Monika Podhorecka1

1Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 2Students Scientific Association, Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 3Department of Clinical Transplantology, Medical University of Lublin, Lublin, Poland

Correspondence: Agnieszka Szymczyk Department of Clinical Transplantology
Medical University of Lublin, Chodźki 7 Street, Lublin, 20-093, Poland
Tel +48-81 534 54 96
Email agnieszka.szymczyk.med@wp.pl

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, p53 protein, molecular aberrations, drug resistance

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