Acute myeloid leukemia 1–eight-twenty-one fusion protein (AML1-ETO)

The acute myeloid leukemia 1–eight-twenty-one fusion protein (AML1–ETO) is an abnormal transcription factor produced by the chromosomal translocation t(8;21)(q22;q22), which fuses the DNA-binding domain of AML1 (also known as RUNX1 or CBFA2) with nearly the entire ETO (also called MTG8 or RUNX1T1) corepressor. This genetic event is found in approximately 40% of French-American-British M2 subtype acute myeloid leukemias and up to 15% overall cases. The resulting chimeric oncoprotein acts as a dominant-negative inhibitor against normal AML1 function, repressing genes critical for hematopoietic differentiation by recruiting corepressors such as histone deacetylase complexes. Functionally, AML1–ETO enhances self-renewal and survival capacity in pluripotent hematopoietic stem cells while inhibiting differentiation and colony formation among committed progenitors. It also disrupts E-protein-mediated gene activation through direct interaction, further contributing to leukemogenesis. Targeted therapies such as oridonin have shown potential by inducing cleavage and functional inhibition of this oncoprotein in preclinical models.

Other names

RUNX1-ETORUNX1–RUNX1T1 fusion proteint(8;21) fusion protein

Inhibition of transcription factor activity via dominant-negative effect on AML1/RUNX1 Recruitment of corepressor complexes, including histone deacetylases, to repress gene expression