{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:59:03Z","timestamp":1790186343809,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Despite the groundbreaking success of tyrosine kinase inhibitor therapy, the management of chronic myeloid leukemia patients is often impaired by resistance due to specific point mutations in the BCR::ABL1 oncogene. Upon classical ATP-competitive inhibitor treatment, these single nucleotide variants occur in the tyrosine kinase domain of ABL1. The novel allosteric BCR::ABL1 inhibitor asciminib was developed to treat CML patients alone or in combination to overcome or potentially prevent these treatment-emergent TKD mutations. Here, we present a case of a patient undergoing first-line asciminib therapy, and subsequently develop a specific BCR::ABL1\/A337V point mutation, which resulted in asciminib resistance. Switching to second-line dasatinib treatment successfully overcame asciminib resistance and helped to achieve a deep molecular response. In case of treatment failures caused by single asciminib-specific point mutations, dasatinib therapy is a feasible choice.<\/jats:p>","DOI":"10.3390\/curroncol32020097","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T12:12:16Z","timestamp":1739362336000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treatment-Emergent Resistance to Asciminib in Chronic Myeloid Leukemia Patients Due to Myristoyl-Binding Pocket-Mutant of BCR::ABL1\/A337V Can Be Effectively Overcome with Dasatinib Treatment"],"prefix":"10.3390","volume":"32","author":[{"given":"Peter","family":"Batar","sequence":"first","affiliation":[{"name":"Division of Hematology, Institute of Internal Medicine, Clinical Center, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Department of Hematology, Faculty of Medicine, Doctoral School of Clinical Sciences, University of Debrecen, H-4002 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Mezei","sequence":"additional","affiliation":[{"name":"Division of Hematology, Institute of Internal Medicine, Clinical Center, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Department of Hematology, Faculty of Medicine, Doctoral School of Clinical Sciences, University of Debrecen, H-4002 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpad","family":"Illes","sequence":"additional","affiliation":[{"name":"Division of Hematology, Institute of Internal Medicine, Clinical Center, University of Debrecen, H-4002 Debrecen, Hungary"},{"name":"Department of Hematology, Faculty of Medicine, Doctoral School of Clinical Sciences, University of Debrecen, H-4002 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/sj.leu.2403426","article-title":"Imatinib therapy in chronic myelogenous leukemia: Strategies to avoid and overcome resistance","volume":"18","author":"Hochhaus","year":"2004","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1016\/j.clml.2015.02.035","article-title":"Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia","volume":"15","author":"Soverini","year":"2015","journal-title":"Clin. 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Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nature21702","article-title":"The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1","volume":"543","author":"Wylie","year":"2017","journal-title":"Nature"},{"key":"ref_8","first-page":"1","article-title":"Progress in the discovery of BCR-ABL kinase inhibitors for the treatment of leukemia","volume":"Volume 3","author":"Waring","year":"2017","journal-title":"Topics in Medicinal Chemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/leu.2016.104","article-title":"European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia","volume":"30","author":"Steegmann","year":"2016","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ccell.2019.08.004","article-title":"Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants","volume":"36","author":"Eide","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1056\/NEJMoa1902328","article-title":"Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure","volume":"381","author":"Hughes","year":"2019","journal-title":"N. 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Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1182\/blood.2024024657","article-title":"Asciminib Monotherapy as Frontline Treatment of Chronic-Phase Chronic Myeloid Leukemia: Results from the ASCEND Study","volume":"144","author":"Yeung","year":"2024","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106458","DOI":"10.1016\/j.leukres.2020.106458","article-title":"The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase","volume":"98","author":"Manley","year":"2020","journal-title":"Leuk. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1182\/blood.2019002969","article-title":"Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study","volume":"135","author":"Soverini","year":"2020","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1038\/s41375-024-02411-7","article-title":"Impact of BCR::ABL1 single nucleotide variants on asciminib efficacy","volume":"38","author":"Innes","year":"2024","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1038\/leu.2017.264","article-title":"Mechanisms of resistance to the BCR-ABL1 allosteric inhibitor asciminib","volume":"31","author":"Qiang","year":"2017","journal-title":"Leukemia"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/2\/97\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:52Z","timestamp":1760027392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/2\/97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,9]]},"references-count":18,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["curroncol32020097"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32020097","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,9]]}}}