Previously, it has been shown that residues W498, W502, D533, E536, and W540 of the t(8;21)-generated RUNX1/ETO fusion protein, located in the NHR2 domain, are essential for the tetramerization of NHR2 (Figure S1B); mutating these ‘hot spot’ residues to alanine resulted in the formation of NHR2-dimers that do not block myeloid differentiation and fail to induce AML in mice16,17. Here, RUNX1T1 is linked to acute myeloid leukemia.