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

J 2021

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

ŠANDOVÁ, Veronika, Gabriela MLADONICKÁ PAVLASOVÁ, Václav ŠEDA, Kateřina AMRUZ ČERNÁ, Sonali SHARMA et. al.

Základní údaje

Originální název

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

Autoři

ŠANDOVÁ, Veronika (203 Česká republika, domácí), Gabriela MLADONICKÁ PAVLASOVÁ (203 Česká republika, domácí), Václav ŠEDA (203 Česká republika, domácí), Kateřina AMRUZ ČERNÁ (203 Česká republika, domácí), Sonali SHARMA (356 Indie, domácí), Veronika PALUŠOVÁ (703 Slovensko, domácí), Yvona BRYCHTOVÁ (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, domácí), S.M. FERNANDES, Anna PANOVSKÁ (203 Česká republika, domácí), Michael DOUBEK (203 Česká republika, domácí), M.S. DAVIDS, J.R. BROWN, Jiří MAYER (203 Česká republika, domácí) a Marek MRÁZ (203 Česká republika, garant, domácí)

Vydání

haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2021, 0390-6078

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Itálie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.047

Kód RIV

RIV/00216224:14740/21:00123375

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3324/haematol.2021.278644

UT WoS

000715742000023

Klíčová slova anglicky

COMPLEMENTEXPRESSIONRITUXIMABANTIGENCELLS

Štítky

14110212, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 22. 12. 2021 16:07, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

802644, interní kód MU

Název: Signaling propensity in the microenvironment of B cell chronic lymphocytic leukemia (Akronym: LeukemiaEnviron)

Investor: Evropská unie, Signaling propensity in the microenvironment of B cell chronic lymphocytic leukemia, ERC (Excellent Science)

Citovat

ŠANDOVÁ, Veronika, Gabriela MLADONICKÁ PAVLASOVÁ, Václav ŠEDA, Kateřina AMRUZ ČERNÁ, Sonali SHARMA, Veronika PALUŠOVÁ, Yvona BRYCHTOVÁ, Šárka POSPÍŠILOVÁ, S.M. FERNANDES, Anna PANOVSKÁ, Michael DOUBEK, M.S. DAVIDS, J.R. BROWN, Jiří MAYER a Marek MRÁZ. IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib. haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2021, roč. 106, č. 11, s. 2995-2999. ISSN 0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2021.278644.

@article{1813380,
   author = {Šandová, Veronika and Mladonická Pavlasová, Gabriela and Šeda, Václav and Amruz Černá, Kateřina and Sharma, Sonali and Palušová, Veronika and Brychtová, Yvona and Pospíšilová, Šárka and Fernandes, S.M. and Panovská, Anna and Doubek, Michael and Davids, M.S. and Brown, J.R. and Mayer, Jiří and Mráz, Marek},
   article_location = {PAVIA},
   article_number = {11},
   doi = {http://dx.doi.org/10.3324/haematol.2021.278644},
   keywords = {COMPLEMENTEXPRESSIONRITUXIMABANTIGENCELLS},
   language = {eng},
   issn = {0390-6078},
   journal = {haematologica},
   title = {IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib},
   url = {https://haematologica.org/article/view/haematol.2021.278644},
   volume = {106},
   year = {2021}
}

TY  - JOUR
ID  - 1813380
AU  - Šandová, Veronika - Mladonická Pavlasová, Gabriela - Šeda, Václav - Amruz Černá, Kateřina - Sharma, Sonali - Palušová, Veronika - Brychtová, Yvona - Pospíšilová, Šárka - Fernandes, S.M. - Panovská, Anna - Doubek, Michael - Davids, M.S. - Brown, J.R. - Mayer, Jiří - Mráz, Marek
PY  - 2021
TI  - IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib
JF  - haematologica
VL  - 106
IS  - 11
SP  - 2995-2999
EP  - 2995-2999
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - COMPLEMENTEXPRESSIONRITUXIMABANTIGENCELLS
UR  - https://haematologica.org/article/view/haematol.2021.278644
N2  - 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.
ER  -

ŠANDOVÁ, Veronika, Gabriela MLADONICKÁ PAVLASOVÁ, Václav ŠEDA, Kateřina AMRUZ ČERNÁ, Sonali SHARMA, Veronika PALUŠOVÁ, Yvona BRYCHTOVÁ, Šárka POSPÍŠILOVÁ, S.M. FERNANDES, Anna PANOVSKÁ, Michael DOUBEK, M.S. DAVIDS, J.R. BROWN, Jiří MAYER a Marek MRÁZ. IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3K delta inhibitor idelalisib. \textit{haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2021, roč.~106, č.~11, s.~2995-2999. ISSN~0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2021.278644.

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