AML1/ETO Translocation Probe Dual Fusion

AML1 (or RUNX1 – Runt related Transcription Factor 1) is fused with ETO (or MTG8) in the t(8;21)(q22;q22) translocation. The rearrangement is observed in ~40% of AML M2 patients and less frequently in subgroups M1 and M4. Overall 7% of AML cases demonstrate the abnormality, the majority of which are de novo. Additional abnormalities occur in 75% of cases, these may be loss of a sex chromosome, del(9q), trisomy 8 or monosomy 7. Three-way variants of this rearrangement and the t(3;21) (AML1/EVI1) show that juxtaposition of AML1 to the derivative chromosome is consistent and therefore the critical rearrangement. AML1 is the most common target for translocations in acute myeloid leukaemia, the breakpoint mainly occurs in the intron between exons 5 and 6 just before the transactivation domain. The fusion protein created contains the DNA-binding domain of AML1 fused to the transcription factors ETO or EVI1 (on chromosomes 8 and 3 respectively). The abnormality can give rise to tumourigenic growth through a number of mechanisms. AML1 activates transcription of reporter genes from Cbf, GM-CSF, CSF1R, or TCRβ sites.

The AML1 probe mix contains a probe 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. Both are labelled in red. For ETO, the probes cover a region 151kb 5’ of ETO, including the marker D8S1950 and a second probe extending from intron 7 of ETO to 127kb beyond the 3’ 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(8;21) fusion.