Abstract
The expansion of a leukemia clone bearing a Bcr-Abl kinase domain mutation is associated with acquired resistance to imatinib and may also predict disease progression in patients with Philadelphia-positive chronic myeloid leukemia (CML). Here we report results of pyrosequencing to quantitate the non-mutated and mutant alleles in 12 CML patients monitored over periods ranging from 11 to 58 months, and describe three contrasting kinetic patterns: Group 1 - in four patients total BCR-ABL transcript numbers remained high with the mutant allele predominating; Group 2 - in four patients the total number of BCR-ABL transcripts fell to low levels but the mutant allele predominated; and Group 3 - in four other patients the total level of transcripts remained high (n=2) or fell (n=2) but the mutant clone persisted at relatively low level. In Group 2 the mutant leukemia clone was presumably still relatively sensitive to imatinib but in Group 1 the leukemia could be classified as resistant. In Group 3 patients the imatinib sensitivity of the leukemia was variable. We conclude that a mutant clone does not necessarily have a proliferative advantage and its presence does not always account for resistance to imatinib. Other mechanisms underlie resistance in at least some patients.
Original language | English (US) |
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Pages (from-to) | 658-663 |
Number of pages | 6 |
Journal | Leukemia |
Volume | 20 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2006 |
Keywords
- BCR-ABL mutants
- CML
- Imatinib
- Kinase mutants
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research