Altered intracellular signaling by imatinib increases the anti-cancer effects of tyrosine kinase inhibitors in chronic myelogenous leukemia cells.

ABSTRACT: Tyrosine kinase inhibitors (TKI), including imatinib (IM), improve the outcome of CML therapy. However, TKI treatment is long-term and can induce resistance to TKI, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKI. Cancer energy metabolism, characterized by abnormal glycolysis, is linked to cancer cell survival. Interestingly, glycolytic activity was suppressed by continuous exposure to IM, and autophagy increased to maintain cell viability by compensating for glycolytic

SUBMITTER: Hirao T 

PROVIDER: S-EPMC5765287 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature