BCR::ABL1 (diagnostic and monitoring testing)

Specialist Integrated Haematological Malignancy Diagnostic Service (SIHMDS) >> Molecular Pathology

The BCR::ABL1 fusion gene is formed by a reciprocal translocation between chromosomes 9 and 22 [t(9;22)]. This reciprocal translocation forms an elongated chromosome 9 and a short chromosome 22, known as the Philadelphia chromosome.

The Philadelphia chromosome harbours the aberrant BCR::ABL1 fusion gene that is detectable in around ~95% of chronic myeloid leukaemia (CML) cases, and, as such, is considered the hallmark diagnostic feature of the disease. However, this is not exclusive to CML and can be identified in around 30% of adult acute lymphocytic leukaemia (ALL) and some rare de novo acute myeloid leukaemia (AML) cases.

BCR::ABL1 screening:
As detection of BCR::ABL1 is diagnostic for CML and prognostic for ALL/AML, suspected patients should be tested for this fusion gene. For diagnostic purposes both cytogenetic studies (FISH and karyotype) and molecular studies (BCR::ABL1 multiplex PCR) should be performed.

The purpose of BCR::ABL1 multiplex PCR is to detect and identify the BCR::ABL1 transcript present resulting from the varying breakpoints in BCR and ABL1. This test is requested on all diagnostic samples as it is important that the fusion sub-type is determined prior to treatment to allow for accurate patient measurable residual disease monitoring.

Measurable residual disease (MRD) monitoring:
Reverse transcription quantitative PCR (RT-qPCR) is the method used to determine copy numbers of ABL1 and BCR::ABL1. We currently monitor patients with major transcripts (e13a2/e14a2), minor transcripts (e1a2), and rare transcripts (e1a3, e6a2, e8a2, e19a2 and e13a3/e14a3). Amongst CML patients, the e13a2/e14a2 transcript is the most frequent; whereas to the e1a2 transcript in Philadelphia positive ALL patients. Results from the RT-qPCR assays are reported as a ratio between BCR::ABL1 and ABL1. The major e13a2 and/or e14a2 transcripts are also reported on the international scale (IS) by use of a laboratory specific conversion factor.

Click here to download the SIHMDS request form

Where a molecular assessment will aid diagnosis or management in the following:

• M84.1/M84.2/M84.23 (CML)
• M89.8/M89.13/M89.106 (AL other)
• M91.8/M91.9/M91.79 (ALL)
• M224.10 (MDS/MPN)

Refer to the NHSE National genomic test directory for cancer

BCR::ABL1 Screening:
14 calendar days
(Note: urgent testing at diagnosis/relapse will be performed by FISH).

BCR::ABL1 Monitoring:
• Urgent: 7 calendar days
• Routine: 14 calendar days

Note: urgency will be determined by the laboratory based on the clinical information provided on the referral.

15-20ml of peripheral blood or 3-5ml bone marrow in EDTA, however smaller volumes may be processed.

Samples for MRD monitoring must be less than 72 hours old (3 days) upon receipt within the laboratory and be received before 14:30pm. Any samples received after 14:30pm will be accessioned the next working day and processed according to that date. Therefore, samples received after 14:30pm on a Friday will be rejected (unless they were taken on the same day). Diagnostic, pre-treatment, relapse or TKD samples must be less than 5 days old upon receipt within the laboratory.

In instances where this is not possible, please send >25ul of cDNA.

For other sample types, please liaise with the laboratory.