BCR, 22q11.22-q11.23, Green
ABL1, 9q34.11-q34.12, Red
The BCR/ABL1 probe mix contains a 169kb green probe centromeric to the BCR gene and covers the genes GNAZ and RAB36. A second green probe covers a 148kb region that includes the telomeric end of the IGLL1 gene and the flanking region beyond. A red probe covers a 346kb region that includes the ABL1 gene. There is an additional red probe that covers a 173kb region and spans the whole ASS1 gene.
The BCR (BCR activator of RhoGEF and GTPase) gene is located at 22q11.23 and the ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) gene is located at 9q34.12. 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)(q34.12;q11.23) 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 and 22q11.23 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.
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