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Volume 26
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10.3390/ijms262311285
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Chronic Myeloid Leukemia and the T315I BCR::ABL1 Mutation

by
Federico Pierro
1,†,
Stefania Stella
2,†,
Manlio Fazio
1,
Sabina Russo
1,
Michele Massimino
3,
Giuseppe Mirabile
1,
Daniela Belletti
4,
Alessandro Allegra
1,‡ and
Fabio Stagno
1,*,‡
1
Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
2
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
3
Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy
4
IRCCS Bonino Pulejo Center, 98124 Messina, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work as co-first authors.
‡
These authors contributed equally to this work as co-last authors.
Int. J. Mol. Sci. 2025, 26(23), 11285; https://doi.org/10.3390/ijms262311285
Submission received: 27 September 2025 / Revised: 16 November 2025 / Accepted: 19 November 2025 / Published: 21 November 2025
(This article belongs to the Special Issue Advancements in Hematology: Molecular Biology and Targeted Therapies)
Versions Notes

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by both an abnormal expansion of the granuloblastic clone and the pathognomonic presence of the Philadelphia (Ph) chromosome that generates the BCR::ABL1 oncoprotein. Despite the surfacing of tyrosine kinase Inhibitors (TKIs) in 2001, which changed the evolution of the disease, resistance due to point mutation or compound alteration during treatment with target therapy may occur. One of the mutations that is still an on-going challenge in clinical and scientific field is the T315I mutation, since it gives patients a poor prognosis attributable to acquired resistance to therapy. In the following narrative review, we will discuss the current knowledge on the T315I mutation, explore the most suitable treatment options, examine the role of third-generation tyrosine kinase inhibitors, and outline potential future therapeutic strategies.
Keywords: Chronic Myeloid Leukemia; BCR::ABL1; CML therapy; T315I mutation; CML mutation; prognosis; acquired resistance Chronic Myeloid Leukemia; BCR::ABL1; CML therapy; T315I mutation; CML mutation; prognosis; acquired resistance

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MDPI and ACS Style

Pierro, F.; Stella, S.; Fazio, M.; Russo, S.; Massimino, M.; Mirabile, G.; Belletti, D.; Allegra, A.; Stagno, F. Chronic Myeloid Leukemia and the T315I BCR::ABL1 Mutation. Int. J. Mol. Sci. 2025, 26, 11285. https://doi.org/10.3390/ijms262311285

AMA Style

Pierro F, Stella S, Fazio M, Russo S, Massimino M, Mirabile G, Belletti D, Allegra A, Stagno F. Chronic Myeloid Leukemia and the T315I BCR::ABL1 Mutation. International Journal of Molecular Sciences. 2025; 26(23):11285. https://doi.org/10.3390/ijms262311285

Chicago/Turabian Style

Pierro, Federico, Stefania Stella, Manlio Fazio, Sabina Russo, Michele Massimino, Giuseppe Mirabile, Daniela Belletti, Alessandro Allegra, and Fabio Stagno. 2025. "Chronic Myeloid Leukemia and the T315I BCR::ABL1 Mutation" International Journal of Molecular Sciences 26, no. 23: 11285. https://doi.org/10.3390/ijms262311285

APA Style

Pierro, F., Stella, S., Fazio, M., Russo, S., Massimino, M., Mirabile, G., Belletti, D., Allegra, A., & Stagno, F. (2025). Chronic Myeloid Leukemia and the T315I BCR::ABL1 Mutation. International Journal of Molecular Sciences, 26(23), 11285. https://doi.org/10.3390/ijms262311285

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