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Peer-reviewedCC BYLeukemia

From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia

  • Andreas Hochhaus1
  • Moshe Talpaz2
  • Giuseppe Nicola Saglio3
  • Jörge E. Cortes4
  • Timothy P. Hughes5
  • Jane F. Apperley6
  • Oliver D. Hantschel7
  • Delphine Réa8
  • Peter Schuld9
  • Hagop M. Kantarjian10
10 affiliations
  1. 1Klinik für Innere Medizin II, Hematology/Oncology, Universitätsklinikum Jena and Comprehensive Cancer Center Central Germany, Campus Jena, Jena, Germany. [email protected]
  2. 2Division of Hematology-Oncology, University of Michigan Rogel Cancer Center; Internal Medicine, University of Michigan, Ann Arbor, MI, USA
  3. 3Department of Clinical and Biological Sciences, University of Turin, Torino, Italy
  4. 4O'Neal Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
  5. 5Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, and Adelaide University, Adelaide, SA, Australia
  6. 6Centre for Haematology, Imperial College London, Hammersmith Hospital, London, and Department of Haematology, Hammersmith Hospital, London, UK
  7. 7Institute of Physiological Chemistry, Faculty of Medicine, Philipps University of Marburg, Marburg, Germany
  8. 8Département d'Hématologie, Hôpital Saint-Louis, APHP, Paris, France
  9. 9Novartis Pharma AG, Basel, Switzerland
  10. 10Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. This alteration gives rise to the BCR::ABL1 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.

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Cite

BibTeXRIS
BibTeX
@article{hochhaus2026from,
  title = {{From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia}},
  author = {Andreas Hochhaus and Moshe Talpaz and Giuseppe Nicola Saglio and Jörge E. Cortes and Timothy P. Hughes and Jane F. Apperley and Oliver D. Hantschel and Delphine Réa and Peter Schuld and Hagop M. Kantarjian},
  journal = {Leukemia},
  year = {2026},
  month = may,
  doi = {10.1038/s41375-026-02984-5},
  url = {https://doi.org/10.1038/s41375-026-02984-5},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia
AU  - Andreas Hochhaus
AU  - Moshe Talpaz
AU  - Giuseppe Nicola Saglio
AU  - Jörge E. Cortes
AU  - Timothy P. Hughes
AU  - Jane F. Apperley
AU  - Oliver D. Hantschel
AU  - Delphine Réa
AU  - Peter Schuld
AU  - Hagop M. Kantarjian
PY  - 2026
DA  - 2026/05/22
JO  - Leukemia
DO  - 10.1038/s41375-026-02984-5
UR  - https://doi.org/10.1038/s41375-026-02984-5
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. This alteration gives rise to the BCR::ABL1 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.
SN  - 0887-6924
SN  - 1476-5551
ER  -