A new inducible model for t(8;21) AML

Faithful and tractable mouse models for t(8;21)‐associated human acute myeloid leukaemia (AML) have been difficult to develop, limiting insight into the malignancy associated with this frequent chromosomal translocation. In this issue of EMBO Molecular Medicine, Cabezas‐ Wallscheid et al. bring us a step closer to this goal with an improved Tet‐inducible mouse model of t(8;21)‐associated AML (Cabezas‐Wallscheid et al, 2013). The t(8;21) is found in approximately 10% of human AML and encodes for the leukaemia fusion protein AML1‐ETO (RUNX1‐RUNX1T1) (Miyoshi et al, 1993). The translocation results in a fusion protein comprised of the amino‐terminal part of RUNX1, including the conserved RUNT domain that is critical for function, and nearly the entire coding region of the ETO (RUNX1T1) protein. RUNX1 forms a heterodimeric transcription factor complex with the CBFb protein. This complex is known as core binding factor (CBF), and both the RUNX1 gene on chromosome 21 and the CBFb gene on chromosome 16 are involved in chromosomal translocations in 15–20% of human AML. CBF is a master regulator of haematopoiesis and knockout of either RUNX1 or CBFb results in embryonic lethality due to failure of definitive haematopoiesis (Chuang et al,