{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:24:02Z","timestamp":1790166242095,"version":"4.1.0"},"reference-count":159,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T00:00:00Z","timestamp":1548115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["702786"],"award-info":[{"award-number":["702786"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT156392"],"award-info":[{"award-number":["PJT156392"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autophagy is an evolutionarily conserved cellular recycling process in cell homeostasis and stress adaptation. It confers protection and promotes survival in response to metabolic\/environmental stress, and is upregulated in response to nutrient deprivation, hypoxia, and chemotherapies. Autophagy is also known to sustain malignant cell growth and contributes to cancer stem cell survival when challenged by cytotoxic and\/or targeted therapies, a potential mechanism of disease persistence and drug resistance that has gathered momentum. However, different types of human leukemia utilize autophagy in complex, context-specific manners, and the molecular and cellular mechanisms underlying this process involve multiple protein networks that will be discussed in this review. There is mounting preclinical evidence that targeting autophagy can enhance the efficacy of cancer therapies. Chloroquine and other lysosomal inhibitors have spurred initiation of clinical trials and demonstrated that inhibition of autophagy restores chemosensitivity of anticancer drugs, but with limited autophagy-dependent effects. Intriguingly, several autophagy-specific inhibitors, with better therapeutic indexes and lower toxicity, have been developed. Promising preclinical studies with novel combination approaches as well as potential challenges to effectively eradicate drug-resistant cells, particularly cancer stem cells, in human leukemia are also detailed in this review.<\/jats:p>","DOI":"10.3390\/ijms20030461","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T03:52:32Z","timestamp":1548301952000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Current Outlook on Autophagy in Human Leukemia: Foe in Cancer Stem Cells and Drug Resistance, Friend in New Therapeutic Interventions"],"prefix":"10.3390","volume":"20","author":[{"given":"Katharina","family":"Rothe","sequence":"first","affiliation":[{"name":"Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada"},{"name":"Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-7340","authenticated-orcid":false,"given":"Xiaoyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada"},{"name":"Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ncb0910-814","article-title":"Eaten alive: A history of macroautophagy","volume":"12","author":"Yang","year":"2010","journal-title":"Nat. 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