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The Philadelphia chromosome in chronic myeloid leukaemia (CML) provided the very first such genetic link to cancer\n                    <jats:sup>1,2<\/jats:sup>\n                    . However, little is known about the trajectory to CML, the rate of\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    clonal expansion and how this affects disease. Using whole-genome sequencing of 1,013 haematopoietic colonies from nine patients with CML aged 22 to 81\u2009years, we reconstruct phylogenetic trees of haematopoiesis. Intronic breaks in\n                    <jats:italic>BCR<\/jats:italic>\n                    and\n                    <jats:italic>ABL1<\/jats:italic>\n                    were not always observed, and out-of-frame exonic breakpoints in\n                    <jats:italic>BCR<\/jats:italic>\n                    , requiring exon skipping to derive\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    , were also noted. Apart from\n                    <jats:italic>ASXL1<\/jats:italic>\n                    and\n                    <jats:italic>RUNX1<\/jats:italic>\n                    mutations, extra myeloid gene mutations were mostly present in wild-type cells. We inferred explosive growth attributed to\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    commencing 3\u201314\u2009years (confidence interval 2\u201316\u2009years) before diagnosis, with annual growth rates exceeding 70,000% per year. Mutation accumulation was higher in\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    cells with shorter telomere lengths, reflecting their excessive cell divisions. Clonal expansion rates inversely correlated with the time to diagnosis.\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    in the general population mirrored CML incidence, and advanced and\/or blast phase CML was characterized by subsequent genomic evolution. These data highlight the oncogenic potency of\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    fusion and contrast with the slow and sequential clonal trajectories of most cancers.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-08817-2","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T11:03:07Z","timestamp":1744196587000},"page":"982-990","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Timing and trajectory of BCR::ABL1-driven chronic myeloid leukaemia"],"prefix":"10.1038","volume":"640","author":[{"given":"Aleksandra E.","family":"Kamizela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3486-3168","authenticated-orcid":false,"given":"Daniel","family":"Leongamornlert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-9167","authenticated-orcid":false,"given":"Nicholas","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0322-8970","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3312-732X","authenticated-orcid":false,"given":"Kudzai","family":"Nyamondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5320-8193","authenticated-orcid":false,"given":"Michael","family":"Spencer Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1923-6614","authenticated-orcid":false,"given":"Jing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Mane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Milne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8672-1906","authenticated-orcid":false,"given":"Timothy","family":"Chevassut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-0510","authenticated-orcid":false,"given":"Peter J.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T.","family":"Ellinor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-161X","authenticated-orcid":false,"given":"Brian J. 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