Coe-binding transcription factors (CBFβ have roles in stem cell self-renewal, tissue differentiation and cancer. They are heterodimeric complexes consisting of two subunits, α and β, in which α subunit binds to DNA, while β subunit is thought to stabilize the DNA binding of α subunit. RUNX1 (also called AML1) is the CBFβsubunit which is predominantly expressed during hematopoietic development.
RUNX1 and CBFβare frequently involved in chromosomal alterations associated with hematopoietic diseases, for example, in t(8;21) and inv(16) acute myeloid leukemia (AML). The translocation involving chromosomes 8 and 21 fuses the RUNX1 and ETO genes, leading to the expression of AML1-ETO. Expression of AML1-ETO oncofusion protein in hematopoietic cells results in a stage-specific arrest of maturation and increased cell survival, predisponsing cell to develop leukemia. We therefore planned to develop RUNX1/CBFβ inhibitors as anti-AML therapy.