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

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Authors

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

Year of publication 2021
Type Article in Periodical
Magazine / Source haematologica
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://haematologica.org/article/view/haematol.2021.278644
Doi http://dx.doi.org/10.3324/haematol.2021.278644
Keywords COMPLEMENTEXPRESSIONRITUXIMABANTIGENCELLS
Description 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 PI3K? 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.
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