{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:25Z","timestamp":1792789645012,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU\u2014PNRR M6C2\u2014Investment 2.1 Enhancement and strengthening of biomedical research","award":["PNRR-POC-2022-12375862"],"award-info":[{"award-number":["PNRR-POC-2022-12375862"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Union\u2014Next Generation EU\u2014PNRR M6C2\u2014Investment 2.1 Enhancement and strengthening of biomedical research","award":["CUP E43C22001080006"],"award-info":[{"award-number":["CUP E43C22001080006"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"TrevisoAIL"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Chromosomal BCR-ABL1 fusions are the defining molecular lesions of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia, and are rarely observed in acute myeloid leukemia. Their detection have transformed treatment paradigms by enabling effective use of specific tyrosine kinase inhibitors (TKIs). Although many BCR-ABL1 rearrangements are identified by standard cytogenetics, a clinically relevant subset is cryptic and can escape detection. High-depth RNA sequencing assays have improved our capacity to detect expressed fusion transcripts. Here, we introduce two myeloid cases in which cryptic BCR-ABL1 rearrangements and precise breakpoints detection required an integrated molecular approach: we describe the initial diagnostic pitfalls, detail the downstream therapeutic and prognostic implications and offer practical recommendations for integrating targeted sequencing and cytogenetics into routine practice. In the first case, a patient initially diagnosed with a myelodysplastic\/myeloproliferative neoplasm was reclassified as CML following the discovery of a cryptic e13a2 BCR-ABL1 rearrangement, enabling effective TKI treatment. In the second case, a previously undetected BCR-ABL1 fusion was identified in a relapsed AML patient, along with additional molecular lesions, underscoring the aggressive nature of the disease. Our findings support a systematic, multimodal screening strategy in patients with atypical presentations to ensure the timely detection of clinically actionable fusion events.<\/jats:p>","DOI":"10.3390\/ijms26188812","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T12:27:41Z","timestamp":1757507261000},"page":"8812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unveiling Cryptic BCR-ABL1 Rearrangements: Diagnostic Challenges and Clinical Impact in Myeloid Malignancies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-9906","authenticated-orcid":false,"given":"Anna","family":"Ferrari","sequence":"first","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Salvesi","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-8220","authenticated-orcid":false,"given":"Eugenio","family":"Fonzi","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Giannini","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, Laboratorio Unico-AUSL della Romagna, 47522 Pievesestina di Cesena, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Tonelli","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, Laboratorio Unico-AUSL della Romagna, 47522 Pievesestina di Cesena, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Zacheo","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1321-8790","authenticated-orcid":false,"given":"Matteo","family":"Paganelli","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9117-2867","authenticated-orcid":false,"given":"Federico","family":"Lo Schiavo","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Rosetti","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pathology, Hub Laboratory, AUSL della Romagna, 47522 Pievesestina di Cesena, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-969X","authenticated-orcid":false,"given":"Giorgia","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Marconi","sequence":"additional","affiliation":[{"name":"Hematology Unit, University of Bologna, S. Maria delle Croci Hospital, 48121 Ravenna, RA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/315550a0","article-title":"Fused transcript of abl and bcr genes in chronic myelogenous leukaemia","volume":"315","author":"Shtivelman","year":"1985","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/315758a0","article-title":"Structural organization of the bcr gene and its role in the Ph\u2032 translocation","volume":"315","author":"Heisterkamp","year":"1985","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1001\/jama.2025.0220","article-title":"Chronic Myeloid Leukemia","volume":"333","author":"Jabbour","year":"2025","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1182\/blood-2010-10-314682","article-title":"Mixed-phenotype acute leukemia: Clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification","volume":"117","author":"Matutes","year":"2011","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107665","DOI":"10.1016\/j.leukres.2025.107665","article-title":"Molecular genetic characterization of mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion","volume":"151","author":"Shi","year":"2025","journal-title":"Leuk. 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