Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications
Table 2
Molecular structure of the t(8;21) fusion protein, the origin of various domains, and the localization of important molecular interactions.
Origin
Domain (alternative nomenclature)
Molecular interactions
N-terminal
AML1
Runt
DNA binding
Binding to CBFβ with formation of heterodimers
Binding of other transcriptional regulators
RUNX1T1-derived domains
NHR1 (eTAFH)
Interacts with the nuclear hormone receptor corepressor
Interaction with the activation domain of E-proteins (E2A and HEB)
NHR2 (HHR)
Mediates oligomerization with itself or other ETO molecules
Interacts with the corepressors Sin3, Gfi1, and histone deacetylases 1 and 3
NHR3 (Nervy)
Interacts with the regulatory subunit of type II cAMP-dependent protein kinase
This domain together with the NHR4 domain is absent in the leukemogenic AE9a splice variant that naturally occurs in primary human AML cells with t(8;21)
NHR4 (MYND)
N-CoR and the silencing mediator of retinoid and thyroid hormone receptor (SMRT); these are associated with HDACs
SON, an RNA/DNA-binding protein
This domain is absent in the leukemogenic AE9a splice variant
