Imatinib Resistance in Chronic Myeloid Leukemia Associated with a D363G BCR::ABL1 Kinase Domain Mutation

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Acquired resistance to tyrosine kinase inhibitors (TKIs) is a significant challenge in managing chronic myeloid leukemia (CML).
• Mutations in the BCR::ABL1 tyrosine kinase domain (KDM) are the primary mechanism of TKI resistance, with most occurring in seven specific codons.
• Understanding rare mutations is crucial for effective CML treatment strategies.

Observation:

• A case of CML is presented with a rare D363G BCR::ABL1 KDM.
• This mutation resulted in a suboptimal response to imatinib, a frontline TKI.
• The patient later achieved a sustained major molecular response after switching to dasatinib.

Findings:

• The D363G mutation confers resistance to imatinib.
• Dasatinib effectively controlled the leukemia in this patient.
• The patient maintained response after switching to bosutinib due to side effects.

Implications:

• This case highlights the importance of identifying rare BCR::ABL1 KDM mutations for personalized CML therapy.
• Effective treatment sequencing with TKIs like dasatinib and bosutinib can overcome resistance.
• Reporting such cases aids in optimizing future management of CML patients with rare mutations.