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.

Basic information

Original name

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

Authors

ŠANDOVÁ, Veronika (203 Czech Republic, belonging to the institution), Gabriela MLADONICKÁ PAVLASOVÁ (203 Czech Republic, belonging to the institution), Václav ŠEDA (203 Czech Republic, belonging to the institution), Kateřina AMRUZ ČERNÁ (203 Czech Republic, belonging to the institution), Sonali SHARMA (356 India, belonging to the institution), Veronika PALUŠOVÁ (703 Slovakia, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), S.M. FERNANDES, Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), M.S. DAVIDS, J.R. BROWN, Jiří MAYER (203 Czech Republic, belonging to the institution) and Marek MRÁZ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.047

RIV identification code

RIV/00216224:14740/21:00123375

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000715742000023

Keywords in English

COMPLEMENTEXPRESSIONRITUXIMABANTIGENCELLS

Abstract

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.

Links

802644, interní kód MU

Name: Signaling propensity in the microenvironment of B cell chronic lymphocytic leukemia (Acronym: LeukemiaEnviron)

Investor: European Union, 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 and 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, vol. 106, No 11, p. 2995-2999. ISSN 0390-6078. Available from: 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 and 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, vol.~106, No~11, p.~2995-2999. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2021.278644.

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