Glycolysis Modulation by METTL7B Shapes Acute Lymphoblastic Leukemia Cell Proliferation and Chemotherapy Response

Acute lymphoblastic leukemia (ALL) is a devastating hematological malignancy characterized by uncontrolled proliferation of immature lymphoid cells. While advances in treatment have improved patient outcomes, challenges remain in enhancing therapeutic efficacy and understanding underlying molecular mechanisms. Methyltransferase-like 7B (METTL7B), known for its methyltransferase activity, has been implicated in various solid tumors, yet its role in ALL remains unexplored. Here, we reveal that high METTL7B expression is correlated with poorer prognosis in ALL patients. Employing genetic manipulation strategies, we demonstrate that METTL7B depletion reduces ALL cell proliferation and enhances chemosensitivity. Mechanistically, we uncover METTL7B's involvement in modulating glycolysis, a crucial metabolic pathway supporting ALL cell growth. Furthermore, METTL7B's methyltransferase activity is identified as a determinant of its impact on glycolysis and proliferation. This study sheds light on METTL7B's multifaceted role in ALL, highlighting its potential as a therapeutic target and offering insights into the metabolic rewiring crucial for ALL progression.