Targeting ULK1 in cancer stem cells: insight from chronic myeloid leukemia

Ianniciello, A. and Helgason, G. V. (2022) Targeting ULK1 in cancer stem cells: insight from chronic myeloid leukemia. Autophagy, 18(7), pp. 1734-1736. (doi: 10.1080/15548627.2022.2041152) (PMID:35227175) (PMCID:PMC9298457)

Abstract

Minimal residual disease (MRD) refers to a low number of cells that persist anti-cancer treatment and is the major cause of relapse in solid cancers and leukemias. In chronic myeloid leukemia (CML), a paradigm for stem cell-driven cancer, MRD is maintained by tyrosine kinase inhibitor (TKI)-insensitive leukemic stem cells (LSCs), which may rely on fundamental metabolic processes to resist drug treatment. Macroautophagy/autophagy is a cytoprotective process that has been highlighted as critical for sustaining LSC survival during TKI treatment in robust experimental models of CML. Our recent study shows that the autophagy-initiating kinase ULK1 is required for maintaining energy and redox balance in CML LSCs. Pharmacological inhibition of ULK1 results in stress-induced differentiation of LSCs, rendering them sensitive to TKI treatment, uncovering a promising strategy for selective eradication of LSCs in CML patients.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Helgason, Professor Vignir and Ianniciello, Ms Angela
• Authors: Ianniciello, A., and Helgason, G. V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Autophagy
• Publisher: Taylor and Francis
• ISSN: 1554-8627
• ISSN (Online): 1554-8635
• Published Online: 01 March 2022
• Copyright Holders: Copyright © 2022 Informa UK Limited, trading as Taylor and Francis Group
• First Published: First published in Autophagy 18(7): 1734-1736
• Publisher Policy: Reproduced in accordance with the publisher copyright policy

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
307077		Targeting Autophagy and Aberrant Metabolism of Leukaemic Stem Cells	Vignir Helgason	Cancer Research UK (CRUK)	C57352/A29754	CS -Translational Research Centre