Resistance-associated mutations in chronic lymphocytic leukemia patients treated with novel agents

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F20%3A73600809" target="_blank" >RIV/61989592:15110/20:73600809 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00098892:_____/20:N0000141

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fonc.2020.00894/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Oncology&id=541145" target="_blank" >https://www.frontiersin.org/articles/10.3389/fonc.2020.00894/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Oncology&id=541145</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2020.00894" target="_blank" >10.3389/fonc.2020.00894</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Resistance-associated mutations in chronic lymphocytic leukemia patients treated with novel agents

Popis výsledku v původním jazyce

Inhibitors of B-cell receptor signaling, ibrutinib and idelalisib, and BCL-2 antagonist, venetoclax, have become the mainstay of treatment for chronic lymphocytic leukemia (CLL). Despite significant efficacy in most CLL patients, some patients develop resistance to these agents and progress on these drugs. We provide a state-of-the-art overview of the acquired resistance to novel agents. In 80% of patients with ibrutinib failure, acquired mutations in BTK and PLCG2 genes were detected. No distinct unifying resistance-associated mutations or deregulated signaling pathways have been reported in idelalisib failure. Acquired mutations in the BCL2 gene were detected in patients who had failed on venetoclax. In most cases, patients who have progressed on ibrutinib and venetoclax experience resistance-associated mutations, often present at low allelic frequencies. Resistance-associated mutations tend to occur between the second and fourth years of treatment and may already be detected several months before clinical relapse. We also discuss the development of next-generation agents for CLL patients who have acquired resistant mutations to current inhibitors.

Název v anglickém jazyce

Resistance-associated mutations in chronic lymphocytic leukemia patients treated with novel agents

Popis výsledku anglicky

Inhibitors of B-cell receptor signaling, ibrutinib and idelalisib, and BCL-2 antagonist, venetoclax, have become the mainstay of treatment for chronic lymphocytic leukemia (CLL). Despite significant efficacy in most CLL patients, some patients develop resistance to these agents and progress on these drugs. We provide a state-of-the-art overview of the acquired resistance to novel agents. In 80% of patients with ibrutinib failure, acquired mutations in BTK and PLCG2 genes were detected. No distinct unifying resistance-associated mutations or deregulated signaling pathways have been reported in idelalisib failure. Acquired mutations in the BCL2 gene were detected in patients who had failed on venetoclax. In most cases, patients who have progressed on ibrutinib and venetoclax experience resistance-associated mutations, often present at low allelic frequencies. Resistance-associated mutations tend to occur between the second and fourth years of treatment and may already be detected several months before clinical relapse. We also discuss the development of next-generation agents for CLL patients who have acquired resistant mutations to current inhibitors.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/NV16-32339A" target="_blank" >NV16-32339A: Vliv funkčních polymorfismů ovlivňujících zánět a oxidační stres na průběh chronické lymfocytární leukémie a volbu individuální léčebné strategie</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Oncology

ISSN

2234-943X

e-ISSN

—

Svazek periodika

2020

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

10

Strana od-do

1-10

Kód UT WoS článku

000549174400001

EID výsledku v databázi Scopus

2-s2.0-85088278017