The red probe mix contains a 348kb probe that spans the ABL1 gene and a 173kb probe that spans the ASS1 gene. The green probe mix contains a 173kb probe centromeric to the BCR gene that spans the GNAZ and RAB36 genes. A second green probe covers a 148kb region telomeric to the BCR gene that spans part of the IGLL1 gene.
The BCR (BCR activator of RhoGEF and GTPase) gene is located at 22q11.2 and the ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) gene is located at 9q34.1. Translocation between these two genes gives rise to the BCR::ABL1 fusion gene, and produces a Philadelphia chromosome; the visible result of this translocation.
The presence of a BCR::ABL1 fusion has important diagnostic and prognostic implications in a number of haematological disorders.
The t(9;22)(q34.1;q11.2) translocation is the hallmark of chronic myeloid leukaemia (CML) and is found in around 90-95% of cases1. The remaining cases have a variant translocation, or have a cryptic rearrangement involving 9q34.1 and 22q11.2 that cannot be identified by routine cytogenetic analysis1.
The BCR::ABL1 fusion can also be found in 25% of adult acute lymphoblastic leukaemia (ALL) and in 2-4% of childhood ALL1. The presence of a BCR::ABL1 fusion has been shown to confer a poor prognosis in ALL in both adults and children1,2. The detection of the abnormality is therefore of high importance for risk stratification, which will influence treatment and management decisions2. In a small number of ALL cases, the translocation does not result in a cytogenetically visible Philadelphia chromosome. In these cases, FISH is essential for highlighting the fusion gene3.
This rearrangement is also seen in rare cases of acute myeloid leukaemia (AML). Philadelphia-positive AML is characterised by its resistance to conventional standard chemotherapy and poor prognosis4, so accurate and rapid identification of this chromosomal abnormality is vital.
The CytoCell® BCR/ABL (ABL1) Translocation, Dual Fusion Probe is a qualitative, non-automated, fluorescence in situ hybridisation (FISH) test used to detect chromosomal rearrangements between the 22q11.2 region on chromosome 22 and the 9q34.1 region on chromosome 9 in Carnoy’s solution (3:1 methanol/acetic acid) fixed haematologically-derived cell suspensions from patients with confirmed or suspected chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL).
This device is designed as an adjunct to other clinical and histopathological tests in recognised diagnostic and clinical care pathways, where knowledge of BCR::ABL1 translocation status would be important for clinical management.
This device is designed to detect rearrangements with breakpoints in the region covered by the red and green clones in this probe set, which includes the BCR and ABL1 regions. Breakpoints outside this region, or variant rearrangements wholly contained within this region, may not be detected with this device.
This device is not intended for: use as a stand-alone diagnostic, use as a companion diagnostic, prenatal testing, population-based screening, near-patient testing, or self-testing.
This device has not been validated for sample types, disease types, or purposes outside of those stated in the intended purpose.
It is intended as an adjunct to other diagnostic laboratory tests and therapeutic action should not be initiated on the basis of the FISH result alone.
Reporting and interpretation of FISH results should be performed by suitably qualified staff, consistent with professional standards of practice, and should take into consideration other relevant test results, clinical and diagnostic information.
This device is intended for laboratory professional use only.
Failure to adhere to the protocol may affect the performance and lead to false positive/negative results.
The quality of the products we have received from CytoCell have been excellent. The FISH probes they provide to us give intense, strong signals and are a pleasure to count. What has really stood out however has been the level of support and assistance provided by CytoCell’s application specialists. The team worked very closely alongside our own during the adoption of this product and spent many hours with us perfecting the technique, going above and beyond what I would expect during the transition period. Source BioScience absolutely demand high quality products and service to be able to deliver our results with confidence, and that is what we have received from CytoCell.
Laboratory Operations Manager, Source BioScience, UK