{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T20:18:42Z","timestamp":1788034722634,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The rarer p190 (e1a2) transcript in chronic myeloid leukemia (CML) is associated with atypical presentations; yet, its biological basis remains poorly understood. Using a cohort of 60 patients including 42 chronic phase patients age\u2010matched 1:1 with 42 e13a2\/e14a2 patients in the chronic phase, we investigated the clinical, genomic, and clonal features of e1a2\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    CML. We identified 60 e1a2\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    CML patients showing distinctive hematologic features including lower leukocyte and platelet counts and higher monocytosis (12.3% vs. 2.0%, P\u2009&lt;\u20090.001). Additional somatic mutations were detected in 37\/42 (88%) e1a2 BCR::ABL1 cases compared with 7\/42 (17%) e13a2\/e14a2\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    cases. The mutational spectrum was dominated by\n                    <jats:italic>ASXL1<\/jats:italic>\n                    and\n                    <jats:italic>TET2<\/jats:italic>\n                    , and closely resembled CMML\u2010like profiles. Genomic breakpoint sequences of 34 e1a2\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    cases showed that\n                    <jats:italic>BCR<\/jats:italic>\n                    and\n                    <jats:italic>ABL1<\/jats:italic>\n                    coordinates were similar to those observed in 394 B\u2010ALL. Longitudinal mutational tracking revealed two distinct clonal architectures. In 71% of patients, mutations disappeared with molecular response, consistent with\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    as the founding event. In contrast, 29% of patients had mutations with stable VAFs, while\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    transcript levels decreased after treatment, indicating that the fusion had been acquired within a pre\u2010existing mutated clone. Single\u2010cell genotyping experiments confirmed these clonal architectures. These patients frequently developed cytopenias under tyrosine kinase inhibitor therapy and half required red blood cell transfusions, reflecting persistence of the ancestral clone rather than\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    \u2010driven disease. These findings show that e1a2\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    CML frequently arises within complex, premutated clonal backgrounds, providing a biological basis for its atypical presentation and heterogeneous treatment response.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70454","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:31:32Z","timestamp":1785767492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonal and genomic determinants of e1a2\n                    <i>BCR::ABL1<\/i>\n                    chronic myeloid leukemia: A Fi\u2010LMC study"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-8694","authenticated-orcid":false,"given":"Benjamin","family":"Podvin","sequence":"first","affiliation":[{"name":"Laboratory of Hematology CHU Lille Lille France"},{"name":"PERSTIM Lab, CRC Lille University of Lille, Inserm Lille France"},{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Nibourel","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology CHU Lille Lille France"},{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Hayette","sequence":"additional","affiliation":[{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"},{"name":"Laboratory of Hematology and Molecular Biology, CHU Lyon Sud Pierre\u2010B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Coiteux","sequence":"additional","affiliation":[{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"},{"name":"Hematology Department Huriez Hospital, CHU Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-7237","authenticated-orcid":false,"given":"Rathana","family":"Kim","sequence":"additional","affiliation":[{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"},{"name":"Hematology Laboratory University Hospital Saint\u2010Louis, AP\u2010HP and EA3518, Universit\u00e9 Paris Cit\u00e9 Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, UMR 1342, Institut de Recherche Saint\u2010Louis, Leukemia Institute Paris Saint\u2010Louis Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Rigolot","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Dulucq","sequence":"additional","affiliation":[{"name":"Institut Bergoni\u00e9, Fi\u2010LMC 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Roche\u2010Lestienne","sequence":"additional","affiliation":[{"name":"PERSTIM Lab, CRC Lille University of Lille, Inserm Lille France"},{"name":"Institut Bergoni\u00e9, Fi\u2010LMC Bordeaux France"},{"name":"Genetics Medical Institute, Hopital Jeanne de Flandre Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Fi\u2010LMC group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_11_3_1","first-page":"85","article-title":"Chromosome studies on normal and leukemic human leukocytes","volume":"25","author":"Nowell PC","year":"1960","journal-title":"J Natl Cancer 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