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However, <jats:italic>ABL1<\/jats:italic> kinase domain (<jats:italic>ABL1<\/jats:italic> KD) mutations confer resistance to several TKIs. These mutations have been extensively studied in chronic myeloid leukemia (CML) but less so in <jats:italic>BCR::ABL1<\/jats:italic>\u2010positive acute lymphoblastic leukemia (ALL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our study aimed to analyze the the <jats:italic>ABL1<\/jats:italic> KD mutations in 97 consecutive newly\u2010diagnosed adults with <jats:italic>BCR::ABL1<\/jats:italic>\u2010positive ALL before therapy, in cytogenetic complete remission and at relapse with next generation sequencing (NGS). The relationship between <jats:italic>ABL1<\/jats:italic> KD mutations and TKI selection was also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Previously unreported <jats:italic>ABL1<\/jats:italic> KD mutations R239G, F401V\/L, R516L and K262T were the most prevalent in pre\u2010therapy and cytogenetic remission samples, whereas T315I\/P and P\u2010loop mutations were most prevalent in relapse samples. R239G, F401V\/L, R516L and K262T are related to the <jats:italic>BCR::ABL1<\/jats:italic> structure, whereas T315I\/P and P\u2010loop mutations directly alter kinase activity. BaF3 cells transfected with <jats:italic>ABL1<\/jats:italic> KD F401V, K262T, R239G, or R516L mutations were resistant to imatinib but strongly inhibited by olverembatinib with IC50 values of 0.73 to 1.52nM. Meanwhile, olverembatinib had advantages in increasing complete molecular response (CMR) and good prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, our findings indicate the prevalence and impact of new <jats:italic>ABL1<\/jats:italic> KD mutations in <jats:italic>BCR::ABL1<\/jats:italic>\u2010positive ALL patients, highlighting the necessity for effective therapies targetingthese mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70317","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T10:40:57Z","timestamp":1729680057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New <i>ABL1<\/i> Kinase Domain Mutations in <i>BCR::ABL1<\/i>\u2010Positive Acute Lymphoblastic Leukemia"],"prefix":"10.1002","volume":"13","author":[{"given":"Zixuan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Hematology, Union 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