Molecular monitoring of chronic myeloid leukemia

The tyrosine kinase inhibitor imatinib mesylate (Gleevec) (formerly STI571) has proven to be an effective and safe new therapy for patients with chronic myeloid leukemia (CML). It has induced short-term hematologic control in many patients with advanced-phase CML, with some patients achieving durable responses. In chronic-phase patients it induces significantly better cytogenetic responses and lower progression rates than interferon-alpha. However, relapse is a significant problem, especially for advanced-phase patients, and imatinib alone appears unlikely to be curative in any patient group. Real-time quantitative polymerase chain reaction (Q-PCR) provides an accurate, sensitive, and noninvasive measure of residual leukemia in patients on imatinib. Levels of BCR-ABL in the blood correlate strongly with the bone marrow cytogenetic results and early measurement can predict subsequent cytogenetic response. Complete molecular responses (no BCR-ABL detected by real-time Q-PCR) are rarely achieved. Sequential real-time Q-PCR studies should facilitate rational patient management and allow comparison of different imatinib-based treatment strategies. It may be possible to define levels of molecular response that predict long-term disease control. In addition, by defining patterns of response, an early indication of imatinib resistance may be detected.