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This rearrangement leads to the fusion of <jats:italic>BCR<\/jats:italic> and <jats:italic>ABL1<\/jats:italic> genes giving rise to a chimeric protein with constitutive kinase activity. Imatinib, a tyrosine kinase inhibitor (TKI), is used as a first\u2010line treatment for CML, though ~40% of CML patients do not respond. Here, using structured illumination microscopy (SIM) and 3D reconstruction, we studied the 3D organization patterns of the <jats:italic>ABL1<\/jats:italic> and <jats:italic>BCR<\/jats:italic> genes, and their chromosome territories (CTs) CT9 and CT22, in CD34+ cells from CML patients that responded or not to TKI. We found that TKI resistance in CML is associated with high levels of structural disruption of CT9 and CT22 in CD34+ cells, increased CT volumes (especially for CT22), intermingling between CT9 and CT22, and an open\u2010chromatin epigenetic mark in CT22. Altogether our results suggest that large\u2010scale disruption of CT9 and CT22 correlates with the clinical response of CML patients, which could be translated into a potential prognostic marker of response to treatment in this disease and provide novel insights into the mechanisms underlying resistance to TKI in CML.<\/jats:p>","DOI":"10.1002\/ijc.33903","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T12:39:53Z","timestamp":1639658393000},"page":"1455-1470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Large\u2010scale topological disruption of chromosome territories 9 and 22 is associated with nonresponse to treatment in <scp>CML<\/scp>"],"prefix":"10.1002","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3122-1055","authenticated-orcid":false,"given":"Eunice","family":"Fabian\u2010Morales","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias 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