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Previous studies have investigated the involvement of mitochondrial dynamics in various cancers, revealing potential therapeutic strategies. However, the impact of <jats:italic>BCR::ABL1<\/jats:italic> on mitochondrial dynamics remains unclear. In this study, we demonstrated that <jats:italic>BCR::ABL1<\/jats:italic> is sufficient to induce excessive mitochondrial fragmentation by activating dynamin\u2010related protein (DRP)1 through the mitogen\u2010activated protein kinase (MAPK) pathway. Leukocytes obtained from patients with CML and the <jats:italic>BCR::ABL1\u2010<\/jats:italic>positive cell lines exhibited increased mitochondrial fragmentation compared to leukocytes obtained from healthy donors and <jats:italic>BCR::ABL1<\/jats:italic>\u2010negative cells. Furthermore, the analysis of <jats:italic>BCR::ABL1<\/jats:italic>\u2010transduced cells showed increased phosphorylation of DRP1 at serine 616 and extracellular signal\u2010regulated kinase (ERK) 1\/2. Moreover, the inhibition of DRP1 and upstream mitogen\u2010activated extracellular signal\u2010regulated kinase (MEK) 1\/2 suppressed mitochondrial fragmentation. Strikingly, DRP1 inhibition effectively reduced the viability of <jats:italic>BCR::ABL1<\/jats:italic>\u2010positive cells and induced necrotic cell death. Additionally, a label\u2010free artificial intelligence\u2010driven flow cytometry successfully identified not only the <jats:italic>BCR::ABL1<\/jats:italic>\u2010transduced cells but also peripheral leukocytes from CML patients by assessing mitochondrial morphological alterations. These findings suggested the crucial role of <jats:italic>BCR::ABL1<\/jats:italic>\u2010induced mitochondrial fragmentation in driving <jats:italic>BCR::ABL1<\/jats:italic>\u2010positive cell proliferation, and the potential use of mitochondrial morphological alterations as a clinical biomarker for the label\u2010free detection of CML cells.<\/jats:p>","DOI":"10.1111\/cas.16424","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T17:39:33Z","timestamp":1733765973000},"page":"673-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>BCR::ABL1<\/i>\u2010induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6772-4882","authenticated-orcid":false,"given":"Kohjin","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Hematology Juntendo University Graduate School of Medicine  Tokyo Japan"},{"name":"System Technologies Laboratory, Sysmex Corporation  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Hematology Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Torii","sequence":"additional","affiliation":[{"name":"Department of Pathological Cell Biology Advanced Research Initiative, Institute of Science Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Pathological Cell Biology Advanced Research Initiative, Institute of Science Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyosumi","family":"Ochi","sequence":"additional","affiliation":[{"name":"Department of Hematology Juntendo University Graduate School of Medicine  Tokyo Japan"},{"name":"Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Hematology Juntendo University Nerima Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"System Technologies Laboratory, Sysmex Corporation  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kawamura","sequence":"additional","affiliation":[{"name":"ThinkCyteK.K.  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