title: An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias.
abstract: 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.
authors.forename: Nisha N
authors.initials: NN
authors.lastname: Barretto
authors.forename: Dean S
authors.initials: DS
authors.lastname: Karahalios
authors.forename: Dewen
authors.initials: D
authors.lastname: You
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hemenway
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C090862:ELL protein, human; D009687:Nuclear Proteins; D010455:Peptides; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D010447:Peptide Hydrolases