title: Techniques for risk stratification of newly diagnosed patients with chronic myeloid leukemia.
abstract: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by BCR-ABL, a constitutively active tyrosine kinase generated as a result of the t(9;22)(q34;q11). The natural history of CML is progression from a relatively benign chronic phase to an acute leukemia termed blast crisis. Imatinib, an inhibitor of BCR-ABL tyrosine kinase activity, has a dramatic effect on the natural history of the disease. Despite the favorable outcomes with imatinib, a subset of patients have primary refractory disease, or experience relapse after an initial response. Recently identified molecular predictors of drug response might help predict outcome with tyrosine kinase inhibitor therapy more accurately than clinical prognostication scores, but have not yet been introduced into clinical routine. These techniques include analysis of drug transport proteins, in vitro drug assays, measurement of imatinib plasma levels, BCR-ABL activity monitoring, and gene expression profiling. In this article we review the current status of these technologies, which may ultimately allow us to tailor therapy to a specific patient.
authors.affiliation: Division of Hematology, University of Utah, Salt Lake City, Utah 84112-5550, USA.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Mitchell
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl