MLL1 (Mixed lineage leukemia 1) is a H3K4 methyltransferase and targeting its enzymatic activity, further as being driven by MLL1/WDR5 protein-protein interaction, has been proposed as a novel therapeutic strategy for the treatment of acute leukemia harboring MLL1 fusion proteins. MM-102 is a peptidomimetic MLL1 antagonist which can disrupt the MLL1/WDR5 interaction with Ki value < 1 nM for binding to WDR5. MM-102 at concentration of 50μM could significantly decrease the expression of HoxA9 and Meis-1, two critical MLL1 target genes in MLL1 fusion protein mediated leukemogenesis, in bone marrow cells transduced with MLL1-AF9 fusion construct post 96-hour treatment. Also, it dose-dependently and selectively inhibited MV4;11 and KOPN8 cell line carrying MLL1-AF4 and MLL1-ENL fusion proteins, respectively, at concentration ranging in 25-100μM for 7 days with apoptosis observed, but not K562 leukemia cell line. Adding MM-102 at concentration of 75μM into somatic cell nuclear transfer embryos culture system could greatly improve porcine somatic cell nuclear transfer effciency and blastocyst quality to make them more similar to in vivo embryos. This may due to the rescue of aberrant gene expression patterns of a series of epigenetic chromatin modifcation enzymes, pluripotent and apoptotic genes at the zygotic gene activation and blastocyst stages through down-regulation of H3K4me3 with MM-102.
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