{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:12:59Z","timestamp":1784380379005,"version":"3.55.0"},"reference-count":75,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-183924,PJT-162131"],"award-info":[{"award-number":["PJT-183924,PJT-162131"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004376","name":"Terry Fox Research Institute","doi-asserted-by":"crossref","award":["1074"],"award-info":[{"award-number":["1074"]}],"id":[{"id":"10.13039\/501100004376","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes. To identify additional drivers of leukemogenesis, we analyzed sequencing data from 1,727 unique individual patients with AML, which revealed mutations in ubiquitin ligase family genes in 11.2% of samples from adult patients with AML with mutual exclusivity. The SKP1\/CUL1\/F-box (SCF) E3 ubiquitin ligase complex gene,\n                    <jats:italic>FBXO11<\/jats:italic>\n                    , was the most significantly downregulated gene of the SCF complex in AML. We found that FBXO11 interacts with and catalyzes K63-linked ubiquitination of LONP1 in the cytosol, to promote LONP1 entry into mitochondria. We show that depletion of\n                    <jats:italic>FBXO11<\/jats:italic>\n                    or\n                    <jats:italic>LONP1<\/jats:italic>\n                    reduced mitochondrial respiration through impaired LONP1 chaperone activity to assemble electron transport chain Complex IV. Reduced mitochondrial respiration secondary to\n                    <jats:italic>FBXO11<\/jats:italic>\n                    or\n                    <jats:italic>LONP1<\/jats:italic>\n                    depletion imparted myeloid-biased stem cell properties in primary CD34\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic stem and progenitor cells (HSPCs) in vitro. In a human xenograft model, depletion of\n                    <jats:italic>FBXO11<\/jats:italic>\n                    cooperated with\n                    <jats:italic>AML1-ETO<\/jats:italic>\n                    and mutant\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    to generate serially transplantable AML. Our findings suggest that reduced FBXO11 cooperates to initiate AML by priming HSPC for myeloid-biased self renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.\n                  <\/jats:p>","DOI":"10.1172\/jci181943","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T17:00:16Z","timestamp":1764090016000},"source":"Crossref","is-referenced-by-count":2,"title":["Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1"],"prefix":"10.1172","volume":"136","author":[{"given":"Hayle","family":"Kincross","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."},{"name":"Experimental Medicine Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chi Angela","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."},{"name":"Department of Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."},{"name":"Experimental Medicine Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben","family":"Duns","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Mey","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zurui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Isak","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harwood","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy T.Y.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Research, BC Cancer Research Institute, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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