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Accession IconGSE79057

Antileukemic Efficacy of BET Inhibitor in a Preclinical Mouse Model of MLL-AF4+ Infant ALL

Organism Icon Homo sapiens
Sample Icon 24 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

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We investigated the anti-leukemic effects of the Bromodomain and Extra Terminal inhibitor I-BET151 on primary MLL-AF4 patient samples, using a xenotransplantation mouse model of MLL+ infant ALL in vivo. We reported that I-BET151 treatment impairs the engraftment and the disease burden of primary MLL+ infant ALL samples transplanted into immunedeficient mice. I-BET151 is able to arrest the growth of leukemic cells by blocking cell division and rapidly inducing apoptosis, through the deregulation of crucial target genes of the BRD4 and HOXA9/HOXA7 network. Moreover I-BET151 sensitizes glucocorticoid-resistant MLL+ cells to Prednisolone. Finally we observed that I-BET151 treatment is even more efficient when used in combination with HDAC inhibitor.
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