BCR/ABL1, Qualitative, Diagnostic Assay
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The t(9;22)/BCR-ABL1 abnormality is associated with chronic myelogenous leukemia (CML) and "Philadelphia positive" acute lymphoblastic leukemia of B-cell lineage (Ph ALL). Very rarely, this abnormality has also been identified in cases of acute myeloid leukemia and T-lymphoblastic leukemia/lymphoma. The fusion gene on the derivative chromosome 22q11 produces a chimeric BCR-ABL1 mRNA transcript and corresponding translated oncoprotein. Despite substantial breakpoint heterogeneity at the DNA level, a consistent set of BCR-ABL1 mRNA transcripts are produced that can be readily and sensitively detected by reverse transcription PCR (RT-PCR) technique. In CML, breakpoints in BCR result in either exons 13 or 14 (e13, e14) joined to exon 2 of ABL1 (a2). The corresponding e13-a2 or e14-a2 BCR-ABL1 mRNAs produce a 210 kD protein (p210). Rare cases of CML are characterized by an e19-a2 type mRNA with a corresponding p230 protein. In Ph ALL, the majority of cases harbor an e1-a2 BCR-ABL1 mRNA transcript, producing a p190 protein. However, chimeric mRNA type is not invariably associated with disease type, as noted by the presence of p210-positive Ph ALL and very rare cases of p190-positive CML. Therefore, positive results from a screening (diagnostic) assay for BCR-ABL1 mRNA need to be correlated with clinical and pathologic findings.
In addition to the main transcript variants described above, rare occurrences of both CML and Ph ALL can have alternative break-fusion events resulting in unusual BCR-ABL1 transcript types. Examples include e6-a2 and BCR exon fusions to ABL1 exon a3 (eg, e13-a3, e14-a3, or e1-a3). In addition to detecting common BCR-ABL1 mRNA transcripts, this assay also can identify these rarer BCR-ABL1 transcript variants and is therefore a comprehensive screen for both usual and uncommon BCR-ABL1 gene fusions in hematopoietic malignancies. Given the nature of genetic events in tumors however, this assay will not identify extremely rare and unexpected BCR-ABL1 events involving other exons (eg, case report level) and is therefore not absolutely specific, but is predicted to detect >99.5% of BCR-ABL1 events. Therefore, it is recommended that for diagnosis, RT-PCR plus a second method (eg, BCR-ABL1 FISH or cytogenetics) should be used. However, this RT-PCR assay is invaluable at diagnosis for identifying the precise BCR-ABL1 mRNA type (eg, for future quantitative assay disease monitoring), which complementary methods cannot.
This assay is intended as a qualitative method, providing information on the presence (and specific mRNA type) or absence of the BCR-ABL1 mRNA. Results from this test can be used to determine the correct subsequent assay for monitoring of transcript levels following therapy (eg, BCRAB, BA190). Because the assay is analytically sensitive, it compensates for situations such as partially degraded RNA quality, or low cell number but it is not intended for quantitative or monitoring purposes.
Diagnostic workup of patients with high probability of BCR-ABL1-positive hematopoietic neoplasms, predominantly chronic myelogenous leukemia and acute lymphoblastic leukemia
When positive, the test identifies which specific mRNA fusion variant is present to guide selection of an appropriate monitoring assay.
If a quantitative monitoring assay is not available for a rare fusion variant, this assay may be of some value for monitoring.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is only qualitative and should not be used for routine (ie, quantitative mRNA level) monitoring. Monitoring of most chronic myeloid leukemia (CML) patients should be performed using BCRAB / BCR/ABL, p210 mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Chronic Myelogenous Leukemia (CML). Monitoring of patients known to carry a p190 fusion should be performed using BA190 / BCR/ABL, p190, mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Assay. If a patient is known to have a rare fusion variant that is not covered by ONE of these monitoring assays, contact Dr. He or Dr. Viswanatha at 800-533-1710 extension 6-5323 to discuss whether this qualitative assay can be used for monitoring.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
A qualitative result is provided that indicates the presence or absence of BCR/ABL mRNA. When positive, the fusion variant is also reported.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Burmeister T, Reinhardt R: A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 2008 Apr;32(4):579-585
2. Melo JV: The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 1996;88(7):2375-2384
3. Melo JV: BCR-ABL gene variants. Baillieres Clin Haematol 1997;10(2):203-222