Regulation of PI3K signaling in T-cell acute lymphoblastic leukemia: A novel PTEN/Ikaros/miR-26b mechanism reveals a critical targetable role for PIK3CD

摘要: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, and T-ALL patients are prone to early disease relapse suffer from poor outcomes. The PTEN, PI3K/AKT Notch pathways frequently altered in T-ALL. PTEN a tumor suppressor that inactivates the PI3K pathway. We profiled miRNAs Pten-deficient mouse identified miR-26b as potentially dysregulated gene. validated decreased expression levels of human cells. In addition, exogenous reduced proliferation promoted apoptosis cells vitro, hindered progression vivo. Furthermore, inhibited pathway by directly targeting PIK3CD, gene encoding PI3Kδ, cell lines. ShRNA for PIK3CD CAL-101, inhibitor, growth increased Finally, we showed induced regulating differential Ikaros isoforms transcriptional regulators miR-26b. These results suggest functions development Further characterization targets may be promising novel therapies.