bcr / abl Gene Rearrangement, Quantitative PCR |
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Test Highlights |
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Clinical Use
| • | Diagnose chronic myelogenous leukemia (CML) |
| • | Identify acute lymphoblastic leukemia (ALL) with t(9;22) bcr/abl rearrangement |
| • | Assess prognosis in patients with ALL |
| • | Monitor the effectiveness of therapy |
| • | Monitor minimal residual disease (MRD) |
| • | Predict early relapse |
Clinical Background
The bcr/abl fusion gene, formed by rearrangement of the breakpoint cluster region (bcr) on chromosome 22 with the c-abl proto-oncogene on chromosome 9, is present in virtually all CML patients. It is also identified in some cases of ALL, in which it is associated with poor prognosis. The t(9;22)(q34;q11) translocation associated with bcr/abl leads to a cytogenetic aberration known as Philadelphia chromosome, although this rearrangement may also be detected in the absence of cytogenetically defined Philadelphia chromosome.
The bcr/abl rearrangement causes production of an abnormal tyrosine kinase molecule with increased activity, postulated to be responsible for the development of leukemia. Four fusion transcripts can result from the bcr/abl rearrangement, depending on the breakpoint on chromosome 22: b2a2, b3a2, e1a2, and e19a2. b2a2 and b3a2 are detected mainly in CML and e1a2 is detected mainly in ALL. e19a2 results from a rare rearrangement detected in CML.
Method
In this quantitative assay, extracted RNA is subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) to amplify 3 types of bcr/abl fusion transcripts: b2a2, b3a2, and e1a2. An additional amplification of the abl gene is performed as a control for sample RNA quality and as a reference for relative quantification. For follow-up and monitoring the effectiveness of treatment, a previous stored sample, if available, will be analyzed along with the current sample to assess quantitative changes with time (trend). If there is no amplification of fused mRNA (BCR:ABL ratio = 0), the result is reported as negative. For samples with positive results, the ratio between the quantities of the fused mRNA (BCR/ABL) and control mRNA (ABL) is reported. The analytical sensitivity of this test is 1 tumor cell in 100,000 normal cells. This assay does not detect the e19a2 transcript.
A reflex test code (15101X) can be ordered to determine the type of translocation. With this test, specimens with positive bcr/abl results are reflexed to an additional PCR assay (at additional charge) to distinguish e1a2 (expressed in ALL) from b2a2 and b3a2 (expressed in CML). Results are reported as positive or negative for e1a2 and b2a2/b3a2.
CPT Codes:* 83891, 83898 x3, 83901, 83902 x2, 83896 x3, 83912
CPT codes for reflex (at additional charge): 83891, 83898 x3, 83896 x6, 83912
Interpretive Information
A positive result indicates the presence of Philadelphia chromosome, but the diagnosis of CML or ALL should be based on the presence of characteristic cellular abnormalities in bone marrow. In patients with ALL, the bcr/abl rearrangement is associated with poor prognosis. Increasing levels of BCR/ABL are associated with clinical progression. To monitor MRD, we recommend evaluating changes with time (trend) rather than the absolute ratio from a single time point.
Specimen Requirements
3 mL room-temperature or refrigerated whole blood in an EDTA (lavender-top) tube; 1 mL minimum.
Alternatively, submit 3 mL bone marrow in an EDTA (lavender-top) tube; 0.5 mL minimum.
Information regarding draw time and date is required to ensure stability of the sample is maintained.
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This test was developed and its performance characteristics determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.
Polymerase chain reaction (PCR) is performed pursuant to a license agreement with Roche Molecular Systems, Inc.
