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Updated: Feb 13, 2026
13:22
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
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Intrinsic cellular resistance to BCR::ABL1 inhibitors
Nataly Cruz-Rodriguez1, Yulieth Torres-Llanos1, Michael W Deininger1
1Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Ann Arbor, MI.
Haematologica
|February 12, 2026
Summary
Chronic myeloid leukemia (CML) treatment with tyrosine kinase inhibitors (TKIs) has improved survival, but resistance persists. Understanding BCR::ABL1-independent resistance mechanisms is crucial for developing new therapies.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myeloid leukemia (CML) treatment, significantly improving patient survival.
- Despite TKI success, challenges like drug resistance and persistent minimal residual disease remain, necessitating further research.
Purpose of the Study:
- To review cell-intrinsic resistance mechanisms in CML, including BCR::ABL1 kinase reactivation and BCR::ABL1-independent pathways.
- To explore how CML escapes TKI effects and to propose the underappreciated role of BCR::ABL1 functions beyond kinase activity.
Main Methods:
- Literature review of cell-intrinsic resistance mechanisms in CML.
- Analysis of BCR::ABL1-driven reprogramming of hematopoietic stem and progenitor cells.
Main Results:
- Patients on TKI therapy show near-normal survival, yet resistance and residual leukemia persist.
- BCR::ABL1-independent resistance mechanisms contribute to TKI failure and disease progression.
- BCR::ABL1 functions beyond kinase activity may be critical in CML pathogenesis.
Conclusions:
- Understanding diverse resistance mechanisms is key to overcoming TKI limitations in CML.
- Targeting BCR::ABL1 functions beyond kinase activity, potentially with degraders, offers a promising therapeutic strategy.
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