beta-Glucuronidase is an optimal normalization control gene for molecular monitoring of chronic myelogenous leukemia.
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.
Lee
Joong Won
JW
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Chen
Qiaofang
Q
Knowles
Daniel M
DM
Cesarman
Ethel
E
Wang
Y Lynn
YL
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
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D005966:Glucuronidase