What Does the BCR/ABL Test Detect?
The BCR/ABL test detects the presence of the BCR-ABL1 fusion gene, which results from the Philadelphia chromosome translocation t(9;22) between chromosomes 9 and 22, and is the diagnostic hallmark of chronic myeloid leukemia (CML). 1, 2
Primary Diagnostic Purpose
The BCR/ABL test identifies the abnormal fusion gene that produces a chimeric protein with deregulated tyrosine kinase activity, which drives the pathogenesis of CML. 1, 2 This fusion gene is present in:
- 95% of chronic myeloid leukemia (CML) cases 1
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) 1, 3
- Rarely in acute myeloid leukemia (AML) 4
Types of BCR-ABL Transcripts Detected
The test identifies different fusion transcript variants based on where the chromosomal break occurs: 1
- e13a2 and e14a2 (b2a2 and b3a2): Most common in CML (~98-99%), encoding the p210 protein, with breakpoints in the major breakpoint cluster region (M-BCR) 1
- e1a2: Encodes p190 protein, typically associated with Ph+ ALL but found in only 1% of CML cases 1
- e19a2: Encodes p230 protein, involving the micro breakpoint cluster region (μ-BCR), associated with enhanced neutrophil differentiation 1
- Atypical variants (e6a2, e8a2, e13a3, e14a3): Found in 1-2% of CML cases 1
Clinical Applications Beyond Diagnosis
Treatment Monitoring
Quantitative RT-PCR (RT-qPCR) measures BCR-ABL1 transcript levels to monitor treatment response to tyrosine kinase inhibitors (TKIs). 1 This is the most sensitive method available, capable of detecting one CML cell among 100,000 or more normal cells. 1
Establishing Treatment Eligibility
The test confirms the presence of typical BCR-ABL transcripts (e13a2/e14a2) required for treatment discontinuation eligibility after achieving sustained molecular response. 5
Detecting Minimal Residual Disease
RT-PCR can identify residual leukemic cells even after achieving complete cytogenetic response, when conventional cytogenetics shows no Philadelphia chromosome. 1, 6
Testing Methodologies
Multiple approaches detect BCR/ABL rearrangements: 1
- Qualitative RT-PCR: Determines the exact BCR-ABL1 transcript type; mandatory for all confirmed CML patients 1
- Quantitative RT-PCR (RT-qPCR): Measures transcript levels using the International Scale for monitoring treatment response 1
- FISH (Fluorescence In Situ Hybridization): Detects BCR/ABL1 rearrangements regardless of breakpoint location, including cryptic translocations not visible by conventional cytogenetics 1, 3, 4
- Conventional cytogenetics: Identifies the Philadelphia chromosome but may miss cryptic rearrangements 1
Critical Clinical Caveat
If using RT-PCR as the primary screening method, the assay must detect both typical AND atypical BCR-ABL1 variants. 1 Screening only for p210 or p210 plus p190 transcripts may result in up to 2% of genuine CML cases being misdiagnosed. 1 Laboratories must clearly state on reports if atypical variants would not have been detected. 1
Therapeutic Significance
Identifying the BCR-ABL1 fusion gene is essential because the BCR::ABL1 protein is the specific molecular target of all tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminib) used to treat CML. 2 Without this fusion gene, these targeted therapies would be ineffective.