一种对混合谱系白血病具有治疗潜力的靶向AF9/ENL的肽。
An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias.
作者信息
Barretto Nisha N, Karahalios Dean S, You Dewen, Hemenway Charles S
出版信息
J Exp Ther Oncol. 2014;10(4):293-300.
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.
摘要
转录延伸的失调被认为是MLL白血病病理生物学的基础。AF4、AF9和ENL是常见的MLL融合伴侣，它们与正性转录延伸因子b（P-TEFb）形成复合物。在这些复合物中，AF9及其同源物ENL直接与AF4相互作用。此前，我们设计了一种模拟AF4的AF9结合域的肽，并报道MLL白血病细胞系受到其抑制。扩展这些研究，我们对肽的设计进行了修改，以避免被蛋白酶识别。该肽在体外与前体肽一样有效，并能提高携带MLL白血病细胞系的小鼠的存活率。
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