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.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30205 Hematology
Country of publisher Italy
Confidentiality degree is not subject to a state or trade secret
WWW 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
Tags 14110212, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 22/12/2021 16:07.
Abstract
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 MUName: Signaling propensity in the microenvironment of B cell chronic lymphocytic leukemia (Acronym: LeukemiaEnviron)
Investor: European Union, ERC (Excellent Science)
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