{"title":"Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells.","authors":"Seiichi Okabe, Mitsuru Moriyama, Akihiko Gotoh","doi":"10.14740/wjon1818","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Asciminib is approved for treating patients with chronic-phase chronic myeloid leukemia who were previously treated with two or more tyrosine kinase inhibitors or those with <i>T315I</i> mutation. However, the mechanisms underlying asciminib resistance remain unclear.</p><p><strong>Methods: </strong>In this study, we established a new asciminib-resistant cell line. We examined <i>BCR::ABL1</i> gene mutation analysis and the effects of conventional chronic myelogenous leukemia inhibitors.</p><p><strong>Results: </strong>Direct sequencing revealed <i>Y139D</i> and <i>T315I</i> mutations in asciminib-resistant cells. Ponatinib and omacetaxine were effective against asciminib-resistant cells.</p><p><strong>Conclusions: </strong><i>Y139D</i> and <i>T315I</i> mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"15 2","pages":"319-324"},"PeriodicalIF":2.1000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965256/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14740/wjon1818","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Asciminib is approved for treating patients with chronic-phase chronic myeloid leukemia who were previously treated with two or more tyrosine kinase inhibitors or those with T315I mutation. However, the mechanisms underlying asciminib resistance remain unclear.
Methods: In this study, we established a new asciminib-resistant cell line. We examined BCR::ABL1 gene mutation analysis and the effects of conventional chronic myelogenous leukemia inhibitors.
Results: Direct sequencing revealed Y139D and T315I mutations in asciminib-resistant cells. Ponatinib and omacetaxine were effective against asciminib-resistant cells.
Conclusions: Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.
期刊介绍：
World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.
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