An AF9/EnL-targted peptide with therapeutic potential in mixed lineage leukemias
Nisha N. Barretto, Dean S. Karahalios, Dewen You and Charles S. Hemenway
Misregulation of transcription elongation is proposed to underlie the pathobiology of MLL leukemia. AF4, AF9, and ENL, common MLL fusion partners, are found in complex with positive transcription elongation factor b (P-TEFb). AF9 and its homolog ENL directly interact with AF4 within these complexes. Previously, we designed a peptide that mimics the AF9 binding domain of AF4 and reported that MLL leukemia cell lines are inhibited by it. Extending these studies, we have modified the peptide design in order to avoid recognition by proteases. The peptide is as effective as its predecessor in vitro and enhances survival in mice bearing MLL leukemia cell lines.
Keywords: Mixed lineage leukemia, leukemia initiating cell, super elongation complex, P-TEFb, HIV Tat, peptide therapeutics, necrosis.