About the Testing | Indication | Testing Methodology | Accuracy | Specimen Requirements | Turnaround Time | CPT Codes | References | Contact Us
The Philadelphia chromosome, a translocation of chromosomes 9:22 that results in the BCR-ABL fusion gene, is present in approximately 95% of chronic myeloid leukemia and 25-30% of adult acute lymphoblastic leukemia cases. If present, the ratio of fusion gene to a reference gene can be used to monitor disease progress. Monitoring the level of BCR-ABL is helpful for both prognosis and management of therapy in patients with disease. Cincinnati Children’s Molecular Genetics Laboratory will use a methodology that measures the number of copies of the BCR-ABL fusion gene (p210) present relative to the number of BCR gene transcripts in the same sample. Comparing the ratio of disease fusion gene copies to normal gene copies allows physicians to have a numerical measure of response to therapy and allows for a more sensitive monitoring for possible disease relapse. A major molecular response is considered to be a 3-log reduction in the ratio from baseline of diagnosis (50% BCR-ABL/BCR ratio must reduce to 0.05% BCR-ABL/BCR ratio or 5 copies of fusion gene compared to 10000 copies of the BCR gene).
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Quantitative BCR-ABL testing is indicated for any patient known to have BCR-ABL fusion gene present by FISH for monitoring of disease. An initial sample should be sent once FISH testing is positive for a baseline measurement. Disease can then be monitored by FISH testing until that result does not indicate presence of fusion gene, and then a quantitative sample should be sent for continued monitoring of disease. This is because the quantitative testing is much more sensitive at measuring small levels of fusion gene products as compared to FISH cytogenetic testing.
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A RQ-PCR reaction is completed on isolated RNA sample using the Ipsogen FusionQuant â Kit. Ipsogen proprietary Fusion Quant® technology precisely quantitates the amount of control and fusion gene transcripts in patient samples by generating standard curves based on the known concentration of plasmid dilutions of both genes. Importantly, the calculation of the ratio of specific fusion gene transcript concentration to endogenous BCR transcript concentration provides a normalized quantification of the specific fusion gene in each assayed sample. Ipsogen’s standardized Fusion Quant® technology has been shown to be highly reproducible in multi-centric studies, and offers ideal calibrators for inter- and intra-laboratory normalization of RQ-PCR analysis.
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Results are reported as the log reduction of the ratio of amount of BCR-ABL fusion transcripts to BCR transcripts. Sensitivity studies within the laboratory have shown that a ratio as low as 10-5 can be detected. This means that 1 cell with the translocation present within 100,000 normal cells can be detected with our assay. Because of variability of the RNA quantity within a specimen and assay variability, only changes of 0.5 log or greater should be considered significant. Therefore results of 1% BCR-ABL/BCR would be considered equivalent to any results between 3% and 0.3%.
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7-10 days
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83891, 83896, 83898, 83902, 83907, 83912
Please contact the laboratory for pricing.
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Please note sample should not be received same day or shipped overnight on ice (do not freeze).
3-5mls peripheral blood OR 3-5mls bone marrow in EDTA tube.
Shipping Requirements: Please enclose oncology test requisition with sample. If local, please call laboratory at 513-636-4474 for local courier pick-up. If not local, place samples in Styrofoam mailer and ship overnight Federal Express on ice to arrive Monday through Saturday.
Ship to:
Cytogenetics and Molecular Genetics Laboratories
3333 Burnet Avenue, NRB 1042
Cincinnati, OH 45229
513-636-4474
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Baccarani M, et al. (2006). Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108:1809.
Beillard E, et al. (2003). Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR)- a European Against Cancer program. Leukemia 17:2474.
Gabert J, et al. (2003). Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia- A Europe Against Cancer Program. Leukemia 17:2318.
Hughes TP, et al. (2003). Frequency of major molecular responses to imatinib or interferon a plus cytarabine in newly diagnosed chronic myeloid leukemia. Blood 103:2873.
Kantarjian H, et al. (2008). Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood 111:1774.
Muller MC, et al. (2008). Harmonization of BCR-ABL mRNA quantification using a uniform multifunctional control plasmid in 3international laboratories. Leukemia 22:96.
Press et al., (2007). A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response (CCR). Clin Cancer Research 13:6136.
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For additional inquiries, contact us:
Phone 513-636-4474
Fax 513-636-4373
Email moleculargenetics@cchmc.org
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