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Previous studies have demonstrated that AML cells expressing FLT3\u2010internal tandem duplication (ITD) are more sensitive to the proteasome inhibitor bortezomib (Bz) than FLT3 wild\u2010type cells, with this cytotoxicity being mediated by autophagy (Atg). Here, we show that proteasome inhibition with Bz results in modest but consistent proteaphagy in MOLM\u201014 leukemic cells expressing the FLT3\u2010ITD mutation, but not in OCI\u2010AML3 leukemic cells with wild\u2010type FLT3. Chemical inhibition of Atg with bafilomycin A simultaneously blocked proteaphagy and resulted in the accumulation of the p62 Atg receptor in Bz\u2010treated MOLM\u201014 cells. The use of ubiquitin traps revealed that ubiquitin plays an important role in proteasome\u2010Atg cross\u2010talk. The p62 inhibitor verteporfin blocked proteaphagy and, importantly, resulted in accumulation of high molecular weight forms of p62 and FLT3\u2010ITD in Bz\u2010treated MOLM\u201014 cells. Both Atg inhibitors enhanced Bz\u2010induced apoptosis in FLT3\u2010ITD\u2010driven leukemic cells, highlighting the therapeutic potential of these treatments.<\/jats:p>","DOI":"10.1002\/2211-5463.12950","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T17:06:48Z","timestamp":1597511208000},"page":"48-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of the proteasome and proteaphagy enhances apoptosis in FLT3\u2010ITD\u2010driven acute myeloid leukemia"],"prefix":"10.1002","volume":"11","author":[{"given":"Rosa G.","family":"Lopez\u2010Reyes","sequence":"first","affiliation":[{"name":"Institute of Advanced Technology and Life Sciences (ITAV) IPBS\u2010Centre de la Recherche Scientifique (CNRS) Universit\u00e9 Toulouse III Paul Sabatier Toulouse France"},{"name":"Cancer Research Center of Toulouse Unit\u00e9 Mixte de Recherche (UMR) 1037 INSERM ERL 5294 Centre de la 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