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This alteration gives rise to the\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    fusion oncogene, whose constitutive tyrosine kinase activity promotes uncontrolled proliferation and survival of leukemic cells. The discovery of this molecular driver laid the foundation for the development of tyrosine kinase inhibitors (TKIs), which transformed CML management from treatment with non-specific modalities to establishing a new paradigm for precision oncology with targeted therapies. Imatinib, the first TKI, demonstrated unprecedented hematologic, cytogenetic, and molecular responses, rapidly becoming the standard of care in CML. Subsequent generations of TKIs were developed to overcome resistance and intolerance to imatinib. These advances improved survival in CML, bringing life expectancy close to that of the general population for the patients who respond to treatment, and shifting treatment goals towards quality of life and the possibility of treatment-free remission (TFR). Landmark discontinuation studies showed that approximately half of eligible patients can maintain TFR. Despite these achievements, important challenges remain, including TKI resistance, safety considerations, and the relatively low proportion of patients who achieve and maintain TFR. Newer-generation TKIs, combination strategies, immunomodulatory approaches, and emerging treatment modalities such as degraders offer promising avenues to further improve outcomes, expand TFR eligibility, ensure optimal quality of life, address resistance mechanisms, and render therapy available and affordable to all patients with CML worldwide.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-02984-5","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:48:26Z","timestamp":1779428906000},"page":"1092-1110","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-0834","authenticated-orcid":false,"given":"Andreas","family":"Hochhaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3361-3981","authenticated-orcid":false,"given":"Moshe","family":"Talpaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-3514","authenticated-orcid":false,"given":"Giuseppe","family":"Saglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge E.","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3730","authenticated-orcid":false,"given":"Timothy","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-1794","authenticated-orcid":false,"given":"Jane","family":"Apperley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-8169","authenticated-orcid":false,"given":"Oliver","family":"Hantschel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Rea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schuld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2984_CR1","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1038\/leu.2017.253","volume":"31","author":"R Hehlmann","year":"2017","unstructured":"Hehlmann R, Lauseker M, Sau\u00dfele S, Pfirrmann M, Krause S, Kolb HJ, et al. 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MT has an unpaid leadership role in the Society of Hematology Oncology (SOHO); has participated in advisory board meetings for Sumitomo; has received research funding from BMS. GS has received fees for consultancy and speaker\u2019s bureau from Ascentage Pharma, Hikma, Novartis. JEC has served as a consultant or in an advisory role for Lilly, Novartis, Terns Pharma, Astellas, Crossbow, Ascentage, Rigel, Sun Pharma, Syndax, Xspray; has received payment for lectures from Novartis, Pfizer, Takeda; has received research funding from AbbVie, Ascentage, Novartis, Sun Pharma, Terns Pharma, CytoAgents; has received stock options from Bio-Path Holdings. TH has received honoraria for advisory boards and symposia from Novartis, Takeda, Terns; has received research funding from Novartis. JA has received honoraria for advisory boards\/consultancies\/speaker\u2019s bureau from Ascentage, Incyte, Novartis, Paladin, Terns; has received institutional research support from Incyte, Pfizer; has received honoraria from Incyte, Novartis has participated in speaker\u2019s bureau for Bristol Myers Squibb, Incyte, Novartis, Pfizer. OH has received funding from Novartis through the European Treatment and Outcome Study for CML (EUTOS); has received speakers\u2019 honoraria from Novartis. DR has participated in advisory board meetings for Ascentage Pharma, Enliven, Novartis, TERNS; has acted as consultant for Novartis, TERNS; has received honoraria from Ascentage Pharma, Enliven, Incyte, Novartis, and TERNS. PS is an employee of Novartis. HK has received honoraria from AbbVie, Amgen, Pfizer, Ascentage Pharma Group, Ipsen, KAHR Medical, Novartis, Shenzhen Target Rx, Daiichih-Sankyo (institutional), Immunogen (institutional); has a consulting or advisory Role for AbbVie; has received institutional research funding from AbbVie, Amgen, Ascentage Pharma, Bristol Myers Squibb, Daiichi Sankyo\/Lilly, Immunogen, Jazz Pharmaceuticals, Novartis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}