title: beta-Glucuronidase is an optimal normalization control gene for molecular monitoring of chronic myelogenous leukemia.
abstract: Quantitative monitoring of breakpoint cluster region (BCR)-Abelson kinase (ABL) transcripts has become indispensable in the clinical care of patients with chronic myelogenous leukemia. Because quantity and quality of RNA in clinical samples are highly variable, a suitable internal normalization control is required for accurate BCR-ABL quantification. However, few studies have examined suitability of the control genes using criteria relevant to residual disease testing. In this study, we evaluated a number of control genes with the application of several novel criteria, including control gene performance on serial patient sample testing and in a residual disease model. We also examined expression of the control genes in BCR-ABL-positive K562 cells in response to Gleevec treatment. We found that beta-glucuronidase is the best control gene among those studied. Importantly, ABL, a widely used control gene, generates misleading BCR-ABL changes that potentially affect the clinical management of chronic myelogenous leukemia patients.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Joong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Qiaofang
authors.initials: Q
authors.lastname: Chen
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
authors.forename: Y Lynn
authors.initials: YL
authors.lastname: Wang
mesh_terms: D001549:Benzamides; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000235:genetics*; D025202:Molecular Diagnostic Techniques / Q000592:standards*; D018365:Neoplasm, Residual / Q000175:diagnosis; D010879:Piperazines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000494:pharmacology; D012015:Reference Standards; D018401:Sample Size
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D005966:Glucuronidase