PKM2 Mediates Chronic Myeloid Leukemia Imatinib Resistance By Regulating Glycolysis Energy Metabolism

Conclusion: Pyruvate kinase M2 (PKM2) acts as an important rate-limiting enzyme in the aerobic glycolytic pathway, and mediates abnormal metabolic pathways which promote tumor cell proliferation, invasion and drug resistance. Compared to the TKI-sensitive primary cell and cell line, PKM2 was increased in the TKI-resistant primary cell and cell line and related to glycolytic level. PKM2 inhibitor can inhibit CML cells growth, induce cell apoptosis, and combined with IM at a low dose can exhibited a synergistic anti-leukemia effect on TKI-resistant cells. Low dose PKM2 inhibitor combined with IM can enhance targeted killing to the CML cells, suggesting that PKM2 protein plays an important role in the formation of drug resistance. After interfering PKM2 protein, it showed a significant downregulated level of glycolysis in the cell line, and the decreased level of P13K/AKT/mTOR signaling pathway. This study demonstrates that PKM2 may be involved in the regulation of energy metabolism in leukemia cells and induce drug resistance.DisclosuresNo relevant conflicts of interest to declare.

Source: Blood - November 21, 2018 Category: Hematology Authors: Tong, L., Xu, N., Zhou, X., Huang, J., wan-Er, W., Chen, C., Liang, L., Liu, Q., Xiaoli, L. Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research