Jak klinicky interpretovat výsledky TP53 analýz u chronické lymfocytární leukemie v kontextu dostupných terapeutických režimů

Česká verze

Authors: B. Kunt Vonková ²; Š. Pavlová ^1,2; J. Malčíková ^1,2; K. Pál ²; Y. Brychtová ¹; A. Panovská ¹; Š. Pospíšilová ^1,2; M. Doubek ^1,2
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; CEITEC – Středoevropský technologický institut, MU, Brno ²
Published in the journal: Transfuze Hematol. dnes,29, 2023, No. 2, p. 117-123.
Category: Souhrnné/edukační práce
doi: https://doi.org/10.48095/cctahd2023prolekare.cz11

Summary

TP53 gene mutations represent the most important adverse prognostic and predictive factor in patients with chronic lymphocytic leukaemia (CLL) and contribute to an overall worse disease course and risk of early relapse or resistance to chemoimmunotherapy. Results to date suggest that first-line chemoimmunotherapy (FCR) results in clonal selection of TP53 aberrant cells, which has an adverse effect on disease prognosis. Recent studies investigating the clonal evolution of TP53 mutations under BCR and Bcl-2 inhibitor therapy do not suggest a similar trend. Next-generation sequencing (NGS) methods are being increasingly used in the clinical diagnosis of TP53 aberrations, achieving sensitivity of allelic frequency detection below 10% compared to standard Sanger sequencing. In recent years, the focus of CLL research has been on TP53 gene mutations with allelic frequencies below 10% and their clinical significance. In the following review article, we summarize the results published so far on the clonal evolution of TP53 gene mutations under different therapeutic regimens, especially with respect to mutations with an allelic frequency < 10% and their clinical interpretation.

Keywords:

chronic lymphocytic leukemia – TP53 mutations – clonal evolution – FCR – BRC and Bcl-2 inhibitors

Zdroje

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