{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T10:04:55Z","timestamp":1766311495145,"version":"3.28.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The clinical management of chronic myeloid leukemia (CML) patients requires the identification of the type of BCR::ABL1 transcript at diagnosis and the monitoring of its expression and potential tyrosine kinase inhibitor (TKI) resistance mutations during treatment. Detection of resistant mutation requires transcript type-specific amplification of BCR::ABL1 from RNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, a custom RNA-based next-generation sequencing (NGS) assay (Dup-Seq BCR::ABL1) that enables (a) the identification of BCR::ABL1 transcript type and (b) the detection of resistance mutations from common and atypical BCR::ABL1 transcript types was developed and validated. The assay design covers BCR exon 1 to ABL1 exon 10 and employs duplicate PCR amplification for error correction. The custom data analysis pipeline enables breakpoint determination and overlapped mutation calling from duplicates, which minimizes the low-level mutation artifacts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This study demonstrates that this novel assay achieves high accuracy (positive percent agreement (PPA) for fusion: 98.5%; PPA and negative percent agreement (NPA) for mutation at 97.8% and 100.0%, respectively) and sensitivity (limit of detection (LOD) for mutation detection at 3% from 10 000 copies of BCR::ABL1 input).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The Dup-Seq BCR::ABL1 assay not only allows for the identification of BCR::ABL1 typical and atypical transcript types and accurate and sensitive detection of TKI-resistant mutations but also simplifies molecular testing work flow for the clinical management of CML patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfae096","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T13:40:47Z","timestamp":1725370847000},"page":"886-900","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Next-Generation Sequencing Assay for the Identification of <i>BCR<\/i>::<i>ABL1<\/i> Transcript Type and Accurate and Sensitive Detection of TKI-Resistant Mutations"],"prefix":"10.1093","volume":"9","author":[{"given":"Zhenyu","family":"Yan","sequence":"first","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Liu","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad","family":"Galderisi","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Spittle","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"ICON Laboratory Services, ICON plc, Cambridge, MA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"2024110323570701800_jfae096-B1","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1182\/blood.V96.10.3343","article-title":"The molecular biology of chronic myeloid leukemia","volume":"96","author":"Deininger","year":"2000","journal-title":"Blood"},{"key":"2024110323570701800_jfae096-B2","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood.V88.7.2375.bloodjournal8872375","article-title":"The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype","volume":"88","author":"Melo","year":"1996","journal-title":"Blood"},{"key":"2024110323570701800_jfae096-B3","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1038\/s41375-023-02048-y","article-title":"European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia","volume":"37","author":"Cross","year":"2023","journal-title":"Leukemia"},{"key":"2024110323570701800_jfae096-B4","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/s41375-018-0341-4","article-title":"The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. 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