title: Molecular monitoring of chronic myeloid leukemia.
abstract: 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.
authors.affiliation: Divisions of Haematology and Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Hughes
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
mesh_terms: D001549:Benzamides; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl