Abstract
BCR-ABL1 compound mutations can lead to resistance to ABL1 inhibitors in chronic myeloid leukemia (CML), which could be targeted by combining the ATP-site inhibitor ponatinib and the allosteric inhibitor asciminib. Here, we report the clinical validation of this approach in a CML patient, providing a basis for combination therapy to overcome such resistance.
Copyright © 2024 Elsevier Inc. All rights reserved.
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Drug Resistance, Neoplasm* / drug effects
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Drug Resistance, Neoplasm* / genetics
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Female
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Fusion Proteins, bcr-abl* / antagonists & inhibitors
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Fusion Proteins, bcr-abl* / genetics
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Humans
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Imidazoles* / pharmacology
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Imidazoles* / therapeutic use
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
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Male
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Mutation*
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Niacinamide / analogs & derivatives
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Protein Kinase Inhibitors* / pharmacology
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Protein Kinase Inhibitors* / therapeutic use
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Pyrazoles
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Pyridazines* / pharmacology
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Pyridazines* / therapeutic use
Substances
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Pyridazines
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ponatinib
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asciminib
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Fusion Proteins, bcr-abl
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Imidazoles
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Protein Kinase Inhibitors
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BCR-ABL1 fusion protein, human
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Niacinamide
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Pyrazoles