Use

Point mutations within the ABL1 kinase domain of the BCR-ABL1 fusion gene frequently cause secondary resistance to tyrosine kinase inhibitor (TKI) therapy. Those patients with a longer duration of CML prior to initiation of imatinib therapy are reported to have a higher incidence of detectable mutations compared to patients with an earlier onset of imatinib therapy. In addition, failure to achieve a major cytogenetic response within the first six months of therapy often reflects the presence of a mutation or a high probability that a mutation will subsequently be detected. Biochemical and cellular assays have demonstrated that the different BCR-ABL1 kinase domain mutations result in varying levels of resistance. Presence of kinase domain mutations are associated with poor prognosis and higher risk of disease progression. The different mutations may require differing strategies to overcome resistance, such as dose escalation, combination therapy or transplantation. Candidates for the BCR-ABL1 kinase domain mutation analysis include: