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Assessment of individual molecular response in chronic myeloid leukemia patients with atypical BCR-ABL1 fusion transcripts: recommendations by the EUTOS cooperative network
Purpose Approximately 1 – 2% of chronic myeloid leukemia (CML) patients harbor atypical BCR-ABL1 transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated rob...
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Published in: | Journal of cancer research and clinical oncology 2021-10, Vol.147 (10), p.3081-3089 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose
Approximately 1
–
2% of chronic myeloid leukemia (CML) patients harbor atypical
BCR-ABL1
transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients.
Methods
BCR-ABL1
transcripts were amplified and sequenced to characterize the underlying fusion. Residual disease monitoring was carried out by RT-qPCR with specific primers and probes using serial dilutions of appropriate
BCR-ABL1
and
GUSB
plasmid DNA calibrators. Results were expressed as log reduction of the
BCR-ABL1/GUSB
ratio relative to the patient-specific baseline value and evaluated as an individual molecular response (IMR).
Results
In total, 330 blood samples (2–34 per patient, median 8) from 33 CML patients (19 male, median age 62 years) were analyzed. Patients expressed seven different atypical
BCR-ABL1
transcripts (e1a2,
n
= 6; e6a2,
n
= 1; e8a2,
n
= 2; e13a3,
n
= 4; e14a3,
n
= 6; e13a3/e14a3,
n
= 2; e19a2,
n
= 12). Most patients (61%) responded well to TKI therapy and achieved an IMR of at least one log reduction 3 months after diagnosis. Four patients relapsed with a significant increase of
BCR-ABL1/GUSB
ratios.
Conclusions
Characterization of atypical
BCR-ABL1
transcripts is essential for adequate patient monitoring and to avoid false-negative results. The results cannot be expressed on the International Scale (IS) and thus the common molecular milestones and guidelines for treatment are difficult to apply. We, therefore, suggest reporting IMR levels in these cases as a time-dependent log reduction of
BCR-ABL1
transcript levels compared to baseline prior to therapy. |
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ISSN: | 0171-5216 1432-1335 |
DOI: | 10.1007/s00432-021-03569-8 |