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Updated: Jun 10, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph+ ALL receiving dasatinib
Ulla Olsson-Strömberg1, Monica Hermansson, Tuija Lundán
1Department of Hematology, University Hospital, Uppsala, Sweden. ulla.olsson.stromberg@akademiska.se
Abstract:
As a result of the excellent responses achieved in chronic phase chronic myeloid leukemia since the introduction of imatinib, sensitive techniques such as reverse transcriptase real-time PCR are warranted to monitor patients receiving tyrosine kinase inhibitors (TKI). Our objective was to determine the value of molecular monitoring Ph-positive leukemias under dasatinib treatment. We used real-time PCR and ABL1 kinase domain sequencing on sequential samples from 11 patients with Philadelphia-positive leukemias who received dasatinib. We were able to detect pre-existing mutations in the kinase domain of BCR-ABL1 in four patients, particularly in patients with high BCR-ABL1 transcript levels. Most mutations disappeared with dasatinib, however, in five patients a clone with T315I appeared during dasatinib treatment. We conclude that sensitive molecular monitoring with real-time PCR for BCR-ABL1 transcripts and mutation screening of the ABL1 kinase domain of patients with Philadelphia-positive leukemias are valuable for patient management, however, mutation findings should be interpreted with caution, as mutant clones not always behave in vivo as predicted by in vitro assays.
Insights
Molecular monitoring of BCR-ABL1 transcripts using real-time PCR and kinase domain sequencing is valuable for managing Philadelphia-positive leukemia patients on dasatinib. Detecting mutations, including the T315I resistance mutation, aids treatment decisions.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Tyrosine kinase inhibitors (TKIs) like imatinib have improved chronic myeloid leukemia treatment.
- Sensitive monitoring techniques are crucial for patients receiving TKIs.
Purpose of the Study:
- To evaluate the utility of molecular monitoring in Philadelphia-chromosome-positive leukemias treated with dasatinib.
- To assess the role of BCR-ABL1 transcript levels and kinase domain mutations during dasatinib therapy.
Main Methods:
- Real-time PCR was used to quantify BCR-ABL1 transcripts.
- ABL1 kinase domain sequencing was performed on sequential patient samples.
- The study included 11 patients with Philadelphia-positive leukemias receiving dasatinib.
Main Results:
- Pre-existing BCR-ABL1 kinase domain mutations were detected in 4/11 patients, often with high transcript levels.
- Most mutations resolved during dasatinib treatment.
- A T315I mutation clone emerged in 5/11 patients during dasatinib therapy.
Conclusions:
- Sensitive molecular monitoring of BCR-ABL1 transcripts and mutations is valuable for managing Philadelphia-positive leukemia patients on dasatinib.
- Interpreting mutation findings requires caution, as in vitro behavior may not reflect in vivo activity.
- Monitoring can identify resistance mutations like T315I, guiding potential treatment adjustments.
