AML1/ETO Translocation, Dual Fusion LPH026 - Detail

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^1,2. 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.

Reference:/Bibliographie/Literatur/Bibliografia

1. Nucifora G, et al., Blood (1995); 86 (1): 1-14.
2. Heim and Mittelman 1995, Willey-Liss, Inc.