Exploring clonal evolution and genetic causes of therapy failure in chronic lymphocytic leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074541" target="_blank" >RIV/65269705:_____/21:00074541 - isvavai.cz</a>

Result on the web

<a href="https://www.abstractsonline.com/pp8/#!/10372/presentation/1198" target="_blank" >https://www.abstractsonline.com/pp8/#!/10372/presentation/1198</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Exploring clonal evolution and genetic causes of therapy failure in chronic lymphocytic leukemia

Original language description

Introduction: In chronic lymphocytic leukemia (CLL), tumor clones with the mutant TP53 gene frequently expand in disease relapse of patients treated with chemoimmunotherapy. Such an event often leads to disease course deterioration and therapy resistance. However, there is a small number of patients harboring stable minor TP53-mutated clones which do not expand even after several therapy lines. We aimed to identify molecular genetic factors affecting CLL clonal evolution in relation to TP53 mutation expansions. Revealing the clonal architecture and a mutational profile of leukemic cells may contribute to optimal therapy tailoring. Materials and Methods: Using whole exome sequencing, we investigated samples from 52 CLL patients with a known clinical course and different scenarios of TP53 mutation expansions. Our cohort included patients treated with standard chemoimmunotherapy, but also with cell signalling inhibitors. Results: We identified mutations in genes associated with CLL, such as SF3B1, ATM, RPS15, MED12, NOTCH1, or NFKBIE, but also a large number of non-recurrent mutations, which expanded or diminished differently after specific types of therapy and in relation to TP53 mutation profiles. We calculated pathway mutation scores and using advanced statistical methods, we defined groups of patients with similar pathway mutation profiles and examined how the groups differed in a clinical course. Conclusion: Our results aid the understanding of molecular grounds of the clonal evolution in CLL, which is necessary for the rational use of available treatment options and for designing of suitable diagnostic panels.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NU21-08-00237" target="_blank" >NU21-08-00237: Advanced sequencing methods for deciphering structural variants in cancer genome</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů