β-Catenin Regulates Glycolytic and Mitochondrial Function in T-Cell Acute Lymphoblastic Leukemia

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by a poor prognosis. β-catenin is implicated in the progression of T-ALL, yet the precise mechanisms of β-catenin involvement in the pathogenesis of T-ALL, particularly concerning metabolic processes, remain inadequately elucidated. Methods: A β-catenin knockout cell line was generated in the human leukemic cell line Jurkat using the CRISPR-Cas9 technique. Subsequently, assays were performed to evaluate cell proliferation, apoptosis, and metabolic activity. Comparative transcriptomic analysis was conducted between control cells and β-catenin knockout cells. Finally, a mouse xenograft model was employed to assess whether β-catenin knockout attenuates tumor growth and infiltration in vivo. Results: The deletion of β-catenin significantly inhibited proliferation and induced apoptosis. Additionally, the silencing of β-catenin led to the inhibition of glycolysis and a reduction in both mitochondrial mass and membrane potential. These results indicate that β-catenin may play a crucial role in regulating cell proliferation and apoptosis through the modulation of glycolytic activity and mitochondrial function in T-ALL. Conclusions: In summary, our findings uncover a novel mechanism by which β-catenin influences glycolysis and mitochondrial function in the progression of T-ALL, thereby identifying a potential therapeutic target for patients with relapsed T-ALL.