{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:56:27Z","timestamp":1790679387825,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial DNA (mtDNA) mutations are frequently observed in cancer, but their clinical and functional significance in chronic myeloid leukemia (CML) remains incompletely defined. Here, we show that a distinct mtDNA mutational landscape is associated with mitochondrial metabolic programs and response to imatinib therapy in CML. We performed comprehensive profiling of somatic mtDNA mutations in 120 patients with chronic\u2010phase CML. At diagnosis, 241 somatic mtDNA mutations were identified in 92 patients, including 29 homoplasmic mutations. In a clinically annotated cohort of 79 imatinib\u2010treated patients, a higher number of mtDNA mutations (\u22653 mutations) and higher variant allele frequency were associated with superior molecular responses, and remained significant in multivariable analyses. mtDNA mutational patterns were associated with distinct metabolic phenotypes in CD34\n                    <jats:sup>+<\/jats:sup>\n                    leukemic stem\/progenitor cells. Suboptimal responders exhibited increased mitochondrial respiration, spare respiratory capacity, mitochondrial content, and enrichment of mitochondrial biogenesis and lipid metabolic programs, consistent with enhanced oxidative phosphorylation dependence. In contrast, favorable responders displayed higher mtDNA mutational burden together with reduced respiratory reserve and increased mitophagy\u2010related programs. Pharmacologic Complex I inhibition reduced clonogenic potential and enhanced imatinib sensitivity. Collectively, these findings identify mtDNA mutational states as a biomarker of metabolic fitness and therapeutic response in CML, while supporting further investigation of mitochondrial metabolism as a potential therapeutic vulnerability in CML.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70429","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:30:51Z","timestamp":1788795051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial DNA mutations are associated with impaired oxidative phosphorylation and enhanced imatinib response in chronic myeloid leukemia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-2966","authenticated-orcid":false,"given":"Ilaria S.","family":"Pagani","sequence":"first","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"},{"name":"Department of Medical Biology University of Melbourne Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaidehi","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Centre for Computational Biology, Program in Cardiovascular and Metabolic Disorders Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Centre for Computational Biology, Program in Cardiovascular and Metabolic Disorders Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung H.","family":"Kok","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Centre for Cancer Biology University of South Australia Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BeiJun","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Computational Biology, Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian Leong","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Computational Biology, Program in Cardiovascular and Metabolic Disorders Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong M.","family":"Pham","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Division Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Page","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong","family":"Dang","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verity A.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"James","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Lim","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mangiola","sequence":"additional","affiliation":[{"name":"Department of Medical Biology University of Melbourne Melbourne Victoria Australia"},{"name":"Bioinformatics and Computational Biology Division Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia"},{"name":"South Australian immunoGENomics Cancer Institute University of Adelaide Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingnan","family":"Gao","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute University of Adelaide Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naranie","family":"Shanmuganathan","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"},{"name":"Centre for Cancer Biology University of South Australia Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Yong","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"},{"name":"Royal Perth Hospital and the University of Western Australia Medical School Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Branford","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Centre for Cancer Biology University of South Australia Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Chuah","sequence":"additional","affiliation":[{"name":"Centre for Computational Biology, Program in Cardiovascular and Metabolic Disorders Duke\u2010NUS Medical School Singapore Singapore"},{"name":"Department of Haematology Singapore General Hospital and National Cancer Centre Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"},{"name":"Centre for Cancer Biology University of South Australia Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"White","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignir G.","family":"Helgason","sequence":"additional","affiliation":[{"name":"Wolfson Wohl Cancer Research Centre, School of Cancer Sciences University of Glasgow Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Thomas","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Tiong","family":"Ong","sequence":"additional","affiliation":[{"name":"Cancer and Stem Cell Biology Signature Research Programme Duke\u2010NUS Medical School Singapore Singapore"},{"name":"Department of Haematology Singapore General Hospital Singapore Singapore"},{"name":"Division of Medical Oncology Duke University Medical Center Durham North Carolina United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, Blood Cancer Program South Australian Health &amp; Medical Research Institute (SAHMRI) Adelaide South Australia Australia"},{"name":"School of Medicine, College of Health Adelaide University Adelaide South Australia Australia"},{"name":"Australasian Leukaemia and Lymphoma Group Melbourne Victoria Australia"},{"name":"Centre for Cancer Biology University of South Australia Adelaide South Australia Australia"},{"name":"Department of Haematology and Genetic Pathology Flinders University and Medical Centre Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90438-0"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02204-y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02341-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0264-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143300"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-02048-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-026-00778-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08817-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.282184"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012127"},{"key":"e_1_2_11_14_1","first-page":"2738","article-title":"A single\u2010cell atlas identifies pretreatment features of primary imatinib resistance in chronic myeloid leukemia","volume":"141","author":"Krishnan V","year":"2023","journal-title":"Blood"},{"key":"e_1_2_11_15_1","first-page":"73","article-title":"Characterization of bone marrow niche in chronic myeloid leukemia patients identifies CXCL14 as a new therapeutic option","volume":"142","author":"Dolinska M","year":"2023","journal-title":"Blood"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.234898"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17183033"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4399"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04842-5"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018196"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0252-4"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01416-w"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.05.009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.08.001"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3966"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0557-x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02374-0"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54443-3"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02935"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt3873"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00378-8"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-2220"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021594"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.002"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10642"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01839-8"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112125"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-161737"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-590315"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.70276"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14829"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02664-w"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-150680"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0052-4"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks918"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-532085"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0645-6"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01393-7"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005514"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01547-9"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4336"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-025-01467-z"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00721-w"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15237-5"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-80226-3"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23680"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-011-1806-5"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124322"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01503-7"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40222-z"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14068"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02103-8"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi5336"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-70399-y"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70429","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hem3.70429","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:57Z","timestamp":1790676657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.70429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":66,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/hem3.70429"],"URL":"https:\/\/doi.org\/10.1002\/hem3.70429","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70429"}}