Ariane Huang, Sofia R Beer, Christopher A Eide, Brian J Druker, Jeffrey W Tyner, Jessica Leonard, Cristina E Tognon
{"title":"Identifying Drug Combination Strategies for <i>ZMYM2: FGFR1</i> Fusion Positive Leukemia.","authors":"Ariane Huang, Sofia R Beer, Christopher A Eide, Brian J Druker, Jeffrey W Tyner, Jessica Leonard, Cristina E Tognon","doi":"10.1080/28354311.2025.2530229","DOIUrl":"https://doi.org/10.1080/28354311.2025.2530229","url":null,"abstract":"<p><p>Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are a class of fusion protein-driven, poor prognosis leukemias. Leukemias harboring FGFR1 fusions have previously been referred to as 8p11.2 myeloproliferative syndrome (EMS) or stem cell leukemia/lymphoma (SCLL) and are currently referred to as Myeloid/lymphoid neoplasms with FGFR1 rearrangement based on the most recent WHO classification system. To identify new therapeutic options for MLN-TK patients, we evaluated clinical and <i>ex vivo</i> drug response data from a <i>ZMYM2:FGFR1</i>-positive patient who was successfully treated with FGFR kinase-targeting inhibitors. After initially responding to ponatinib, the patient was switched to pemigatinib which eventually transitioned them to a successful transplant. Leukemia cells isolated from the patient exhibited ex vivo sensitivity to ponatinib, bortezomib and axitinib. ZMYM2:FGFR1-transformed Ba/F3 cells were exquisitely sensitive to next generation FGFR inhibitors, and combinations of FGFRi plus trametinib or midostaurin were found to be synergistic, suggesting novel therapeutic options for FGFR1-fusion positive patients.</p>","PeriodicalId":521021,"journal":{"name":"Precision oncogenomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}