FOXO1-RICTOR AXIS induces adaptive increase in AKT activity during BCR inhibitor therapy in CLL: Implications for combination therapy.
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Year of publication | 2023 |
Type | Conference abstract |
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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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