IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074846" target="_blank" >RIV/65269705:_____/21:00074846 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/21:00123375

Výsledek na webu

<a href="https://haematologica.org/article/view/haematol.2021.278644" target="_blank" >https://haematologica.org/article/view/haematol.2021.278644</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2021.278644" target="_blank" >10.3324/haematol.2021.278644</a>

Jazyk výsledku

angličtina

Název v původním jazyce

IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib

Popis výsledku v původním jazyce

Efforts to combine anti-CD20 antibodies (such as rituximab or obinutuzumab) with BCR inhibitors or venetoclax lead to the necessity to better understand the largely unclear mechanisms of CD20 regulation and its function (s) (reviewed in Pavlasova and Mraz1). This is underscored by the observation that in chronic lymphocytic leukemia (CLL) the combination of ibrutinib with rituximab fails to provide a clinical benefit in comparison to ibrutinib alone2 likely as ibrutinib downmodulates CD20 levels.1,3-5 PI3Kδ inhibitor idelalisib has been approved in combination with rituximab or ofatumumab;6 however, it remains unclear if idelalisib affects CD20 levels or function (s). Here we show for the first time that single-agent idelalisib therapy in CLL leads to CD20 downmodulation in vivo by interfering with a previously unknown mechanism of CD20 transcriptional regulation via the IL4- STAT6 axis. We describe a novel mechanism of CD20 regulation in CLL B cells, which has implications for combinatorial therapy with PI3K inhibitors.

Název v anglickém jazyce

IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib

Popis výsledku anglicky

Efforts to combine anti-CD20 antibodies (such as rituximab or obinutuzumab) with BCR inhibitors or venetoclax lead to the necessity to better understand the largely unclear mechanisms of CD20 regulation and its function (s) (reviewed in Pavlasova and Mraz1). This is underscored by the observation that in chronic lymphocytic leukemia (CLL) the combination of ibrutinib with rituximab fails to provide a clinical benefit in comparison to ibrutinib alone2 likely as ibrutinib downmodulates CD20 levels.1,3-5 PI3Kδ inhibitor idelalisib has been approved in combination with rituximab or ofatumumab;6 however, it remains unclear if idelalisib affects CD20 levels or function (s). Here we show for the first time that single-agent idelalisib therapy in CLL leads to CD20 downmodulation in vivo by interfering with a previously unknown mechanism of CD20 transcriptional regulation via the IL4- STAT6 axis. We describe a novel mechanism of CD20 regulation in CLL B cells, which has implications for combinatorial therapy with PI3K inhibitors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/NU20-03-00292" target="_blank" >NU20-03-00292: PRIORITIZACE KOMBINACÍ LÉČIV U CHRONICKÉ LYMFOCYTÁRNÍ LEUKÉMIE NA ZÁKLADĚ ANALÝZY ADAPTACE BUNĚK NA IBRUTINIB A IDELALISIB IN VIVO</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Haematologica

ISSN

0390-6078

e-ISSN

—

Svazek periodika

106

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

IT - Italská republika

Počet stran výsledku

5

Strana od-do

2995-2999

Kód UT WoS článku

000715742000023

EID výsledku v databázi Scopus

2-s2.0-85113352904