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In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E\u22124 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r\u2009=\u20090.858, p\u2009&lt;\u20090.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n\u2009=\u200967 for CML and n\u2009=\u200962 for B-ALL patients). A total of 162 samples (n\u2009=\u200986 CML and n\u2009=\u200976 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    \u2009&lt;\u20091%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E\u22124 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-17271-3","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T10:03:58Z","timestamp":1659089038000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic 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