Clinical Information

The t(9;22)/BCR-ABL1 abnormality is associated with chronic myeloid 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 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 nearly always 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, although some ALL patients may alternatively present with the e13/e14-a2 (p210) type fusion.

This assay provides information at the time of diagnosis regarding the presence (and specific mRNA type) or absence of the BCR-ABL1 mRNA. If positive, the reflex test will follow to provide an initial quantitative level of the specific BCR-ABL1 transcript. For example, when positive for the e1-a2 (p190) type mRNA, the reflex test provides a corresponding p190 quantitative value. Results from this test are also useful to determine the correct quantitative assay for subsequent monitoring of transcript levels (ie, p190 or p210) during tyrosine kinase inhibitor therapy.