The BCR/ABL1 probe mix contains a 169kb green probe centromeric to the BCR gene and contains the genes GNAZ and RAB36. A second green probe covers a 148kb region telomeric to the BCR gene and covers part of the IGLL1 gene. A red probe covers a 346kb region that spans the ABL1 gene. There is an additional blue 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, the ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) gene is located at 9q34.12 and the ASS1 (argininosuccinate synthase 1) gene is located at 9q34.11. Translocation between BCR and ABL1 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%1 of cases. The remaining cases have a variant translocation, or have a cryptic translocation between 9q34.12 and 22q11.23 that cannot be identified by routine cytogenetic analysis1. BCR-ABL1 fusions can also be found in 25% of adult acute lymphoblastic leukaemia (ALL) and in 2-4% of childhood ALL1. This rearrangement is also seen in rare cases of acute myeloid leukaemia (AML)2.
The translocation between chromosomes 9 and 22 can be accompanied by loss of proximal sequences on the derivative chromosome 9, including the ASS1(argininosuccinate synthase 1) region3. Concomitant ASS1 gene deletions have been associated with poorer prognosis in CML, although this may be partially abrogated by treatment with tyrosine kinase inhibitors (TKIs)4; therefore, the establishment of atypical patterns in patients with the BCR-ABL1 translocation may have clinical diagnostic and prognostic implications.
Not only do CytoCell offer an extensive range of high-quality FISH probes, the customer support is also excellent — providing fast access to all the probes I need. The probes are highly consistent with bright signals allowing easy scoring of results.
Dr Eric Crawford
Senior Director, Genetics Associates Inc., USA