Paper: New paper from the Helgason lab - autophagy inhibtion and CML

Paper: New paper from the Helgason lab – autophagy inhibtion and CML

In this paper from the Helgason lab, it is shown that autophagy inhibition results in a metabolic switch from aerobic glycolysis to mitochondrial respiration, positioning autophagy as an important factor in maintaining the Warburg effect in leukaemic cells. They also show that autophagy inhibition and elevated mitochondrial oxidative phosphorylation leads to ROS accumulation in CML cells. This is followed by differentiation of CML cells towards the erythroid lineage. Of clinical importance, the authors show that specific autophagy inhibition, mediated by knockdown of ATG7, sensitises CML cells to tyrosine kinase inhibitor (TKI)-induced death, without affecting survival of normal cells. This indicates that specific autophagy inhibition should achieve selectivity towards leukaemic over normal cells, further supporting the perception that combined inhibition of autophagy with TKI treatment is a potential therapeutic approach for patients who currently need to continue TKI treatment indefinitely with the risk of toxicity, acquired drug-resistance and potential relapse.

 

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Helgason paper figure