FOXO1-RICTOR AXIS induces adaptive increase in AKT activity during BCR inhibitor therapy in CLL: Implications for combination therapy.

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Authors

ONDRIŠOVÁ Laura ŠEDA Václav CHIODIN Giorgia HLAVÁČ Kryštof KOŠŤÁLOVÁ Lenka FILIP Daniel FARIA ZENI Pedro PANOVSKÁ Anna PLEVOVÁ Karla POSPÍŠILOVÁ Šárka ŠIMKOVIČ Martin VRBACKÝ Filip LYSÁK Daniel FERNANDEZ Stacey M. DAVIDS MS. MAIQUES-DIAZ Alba CHARALAMPOPOULOU Stella MARTIN-SUBERO Jose I. BROWN Jennifer R. DOUBEK Michael FORCONI Francesco MAYER Jiří MRÁZ Marek

Year of publication 2023
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

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Description Genetic mechanisms of resistance to BCR inhibitors in CLL have been extensively described. However, it remainsunknown whether non-genetic adaptation mechanisms to BTK inhibitors might exist. We focused on the possible role of the Akt pathway in adapting to BCR inhibitors since, in mouse models, PI3K-Akt activation is the only known factor that rescues the apoptosis induced by BCR deletion in mature B cells. We aim to describe non-genetic mechanisms of adaptation to BCR inhibitor therapy. We performed transcriptome profiling (Illumina) and analyzed samples obtained from CLL patients before and during ibrutinib or idelalisib therapy and performed gene editing in MEC1 cells to reveal the functional role of FoxO1/Rictor.
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