FOX01-rictor AXIS induces AKT phosporylation during CLL cell adaptation to BCR inhibitors: Implications for combinatorial therapy.

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Authors

ONDRIŠOVÁ Laura ŠEDA Václav HOFERKOVÁ Eva CHIODIN G. HLAVÁČ Kryštof KOŠŤÁLOVÁ Lenka MLADONICKÁ PAVLASOVÁ Gabriela FILIP Daniel FARIA ZENI Pedro OPPELT Jan PANOVSKÁ Anna PLEVOVÁ Karla POSPÍŠILOVÁ Šárka SIMKOVIC M. VRBACKÝ F. LYSÁK Daniel FERNANDES SM. DAVIDS MS. MAIQUES-DIAZ A. CHARALAMPOPOULOU S. MARTIN-SUBERO JI. BROWN JR. DOUBEK Michael FORCONI F. 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 Although genetic mechanisms of resistance to BCR inhibitors in CLL are well-known, it remains elusive whether non genetic adaptation mechanisms might exist. We focused on the possible role of Akt pathway as PI3K-Akt activation is the only known factor that rescues the apoptosis induced by BCR deletionin mature Bcells in mouse models. We performed transcriptome profiling (Illumina) and analyzed samples obtained from CLL patients before andduring ibrutinib or idelalisib therapy (1–12weeks of therapy, n=70 patients with 194samples) and performed gene editing in MEC1 cells to reveal the functional role of FoxO1/Rictor.
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