Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia

// Lisa Richter 1,* , Yiqian Wang 1,* and R. Katherine Hyde 1 1 Department of Biochemistry and Molecular Biology and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA * These authors contributed equally to this work Correspondence to: R. Katherine Hyde, email: // Keywords : inv(16), CBFβ-SMMHC, CBFβ, RUNX1, AML Received : March 14, 2016 Accepted : August 09, 2016 Published : August 17, 2016 Abstract Inversion of chromosome 16 (inv(16)) generates the CBFβ-SMMHC fusion protein and is found in nearly all patients with acute myeloid leukemia subtype M4 with Eosinophilia (M4Eo). Expression of CBFβ-SMMHC is causative for leukemia development, but the molecular mechanisms underlying its activity are unclear. Recently, there have been important advances in defining the role of CBFβ-SMMHC and its binding partners, the transcription factor RUNX1 and the histone deacetylase HDAC8. Importantly, initial trials demonstrate that small molecules targeting these binding partners are effective against CBFβ-SMMHC induced leukemia. This review will discuss recent advances in defining the mechanism of CBFβ-SMMHC activity, as well as efforts to develop new therapies for inv(16) AML.