Structural basis of multimer-mediated mayhem

Oligomerization of AML1-ETO contributes to leukemogenesis through obscure mechanisms. In this issue of Cancer Cell, Bushweller and colleagues show the crystal structure of the ETO NHR2 domain to be a tetramer. Tetramer formation is important for maturation arrest and self-renewal, and gene expression is altered in the absence of self-association. Loss of oligomer formation disrupts interactions between AML1-ETO and members of the ETO corepressor family, but not other corepressor molecules posited to be important for leukemogenesis. The findings clarify the role of oligomer formation in AML1-ETO function and suggest a possible therapeutic strategy of targeting ETO-corepressor interactions.