TEL/AML1 Translocation Probe Dual Fusion

The TEL (or ETV6 - Erythroblastosis Variant Gene 6 translocation, ETS) / AML1 (or RUNX1 - Runt-Related Transcription Factor 1) fusion is brought about by the cytogenetically invisible t(12;21) translocation. The rearrangement is the most common in childhood B-ALL and has been detected, using FISH, in around 21% of cases, compared to a pick-up rate of 0.05% by conventional cytogenetics. The translocation is associated with a favourable outcome, though it has also been implicated with late relapse. TEL1 has also been shown to be deleted in some children with ALL where the deletion is cytogenetically invisible but where there is loss of heterozygosity (LOH) of chromosome 12p12-13 and that this deletion is often associated with a TEL1/AML1 translocation. Both the TEL1 and AML1 genes are transcription factors but TEL1 has been shown to be required specifically for proper transcription during Haematopoiesis with the bone marrow. The translocation results in an almost intact AML1 protein, fused with part of the TEL1 protein, resulting from breakpoints beyond exon 4 in TEL1 and 3’ of the AML1 gene.

The ETV6 probe mix contains a probe 5’ of ETV6 covering a region between the marker D12S845 and the 5’ end of intron 2, measuring 182kb and a second probe covering a region 3’ of the gene extending 170kb from the marker D12S1898. Both are labelled in red. For AML, the probes cover 151kb 3’ of RUNX1, including CLIC6 and a second probe extending from intron 3 of RUNX1 to 51kb beyond the 5’ end of the gene. In the normal cell, these probes will appear as discrete red and green spots, one for each homologue (resulting in a 2G 2R conformation). This probe set will detect the t(12;21) fusion and may also detect larger deletions of the TEL1 (ETV6) gene.