Constant BCR-ABL transcript level ≥0.1% (IS) in patients with CML responding to imatinib with complete cytogenetic remission may indicate mutation analysis
Received 13 August 2009; received in revised form 8 October 2009; accepted 12 October 2009. published online 19 October 2009.
Objective
Of 140 chronic myeloid leukemia patients responding to imatinib with complete cytogenetic remission, 32 exhibited a plateau of BCR-ABL values at ≥0.1% level in a minimum of three subsequent samples (minimal duration, 6 − 9 months). Median follow-up of unchanged BCR-ABL transcript level was 12 months (range, 6 − 64). We tested this group of patient for BCR-ABL mutations to reveal resistance development and to evaluate the risk of disease progression.
Materials and Methods
Altogether, 134 samples of peripheral blood of these 32 patients were tested for mutation in BCR-ABL kinase domain.
Results
Mutation was detected by direct sequencing in 9 of 32 patients (28%). Loss of complete cytogenetic remission or 1 log rise of BCR-ABL was observed in five of nine patients at a median of 5 months (range, 4−17) since first detection of mutation. One patient with no mutation relapsed 12 months after the start of the BCR-ABL plateau. In 5 of 32 patients without mutation (16%), BCR-ABL level significantly decreased after the first plateau to levels that stayed unchanged for a median of 11 months (range, 7−28).
Conclusion
We show here that the BCR-ABL constant levels ≥0.1% (BCR-ABL plateau) in imatinib-responding patients may indicate mutation analysis. This approach highly reduces the number of examinations for mutation in chronic myeloid leukemia responders and may present cost-effective alternative applicable in clinical practice.
aInstitute of Hematology and Blood Transfusion, Department of Molecular Genetics, Prague, Czech Republic
bInstitute of Hematology and Blood Transfusion, Clinical Department, Prague, Czech Republic
cDepartment of Internal Medicine, Hematology and Oncology, Center of Molecular Biology and Gene Therapy, Faculty Hospital Brno and Masaryk University, Brno, Czech Republic
dDepartment of Internal Medicine, Hematology and Oncology, Faculty Hospital Brno and Masaryk University, Brno, Czech Republic
eDepartment of Mathematics and Statistics, Faculty of Science, Masaryk University, Brno, Czech Republic
Offprint requests to: Kateřina Machová Poláková, Ph.D., Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, U Nemocnice 1, 128 20 Praha, Czech Republic
ABSTRACT