BCR-ABL1 Testing: What Is It and Why Is It Done?

When a blood test or a bone marrow biopsy leads to a suspected diagnosis of chronic myeloid leukemia (CML) or a specific subtype of acute lymphoblastic leukemia (ALL), one of the primary investigations that follows is a test for the BCR-ABL1 fusion gene. This test sits at the center of both diagnosis and ongoing clinical management for these blood cancers. Understanding what it measures helps patients and families navigate a complex diagnostic process.

The BCR-ABL1 fusion gene results from a chromosomal rearrangement known as the Philadelphia chromosome [t(9;22)], where a piece of chromosome 9 breaks off and fuses with a piece of chromosome 22. This fusion gene produces an abnormal tyrosine kinase protein that drives uncontrolled white blood cell proliferation. Crucially, the same molecular abnormality causing the disease is also the direct target for tyrosine kinase inhibitor (TKI) therapies such as imatinib, dasatinib, and nilotinib.

What the Test Detects

The BCR-ABL1 test detects the presence of the fusion gene and, in its RT-qPCR (Real-Time Quantitative Reverse Transcription PCR) form, measures the precise quantity of the abnormal transcript present in a blood or bone marrow sample. This measurement, reported on the International Scale (% IS), allows hematologists to monitor therapeutic response over time.

• Baseline Assessment: At initial diagnosis, the BCR-ABL1 transcript level establishes a baseline.
• Treatment Monitoring: As treatment progresses, transcript levels drop according to standardized milestones at 3, 6, and 12 months to verify therapeutic efficacy.

The BCR-ABL1 test offered through MedGenome utilizes standardized RT-qPCR methodology aligned with the International Scale (IS), ensuring reporting matches guidelines used in global clinical trials and diagnostic frameworks.

Why Regular Monitoring Matters

A patient’s BCR-ABL1 level at defined intervals is a crucial clinical decision point:

• Assessing Molecular Milestones: Guidelines define optimal response targets (such as Major Molecular Response, or MMR/MR3.0).
• Identifying Resistance: If transcript levels fail to drop or begin rising again, it signals that leukemic cells may have developed drug resistance.
• Kinase Domain Mutation Analysis: Resistance typically stems from point mutations in the BCR-ABL1 kinase domain. When quantitative PCR indicates an inadequate response, MedGenome’s BCR-ABL1 Kinase Domain Mutation Analysis can identify specific mutations (e.g., T315I) to guide the selection of an effective second- or third-generation TKI.

Because molecular changes often precede clinical symptoms or visible blood count changes, relying solely on complete blood counts (CBC) can obscure underlying relapse. Regular molecular monitoring provides the actionable data necessary to maintain long-term disease control.

The BCR-ABL1 genetic test with mutation analysis capability provides the additional detail needed when standard quantitative monitoring suggests inadequate response and a change in treatment approach is being considered.