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-cell lymphoblastic leukemia/lymphoma. The fusion gene on the derivative chromosome 22q11 produces a chimeric BCR::ABL1 messenger RNA (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 polymerase chain reaction (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 kDa 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 greater than 99.5% of BCR::ABL1 events. Therefore, it is recommended that for diagnosis, RT-PCR plus a second method (eg, BCR::ABL1 fluorescence in situ hybridization 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 / BCR/ABL1, p210, mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Chronic Myeloid Leukemia (CML), Varies; BA190 / BCR/ABL1, p190, mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Assay, Varies). 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.
This test was developed and its performance characteristics determined by Marshfield Labs. It has not been cleared or approved by the US Food and Drug Administration. This test is used for clinical purposes. It should not be regarded as investigational or for research.