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Letters to the Editor
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Figure 2. Aberrant BRD4 binding in MLL-partial tandem duplication cells drives a distinct gene expression profile that can be restored by JQ1 treatment. (A) Venn diagram showing overlap of BRD4 binding sites between CD34+ selected cord blood (CB) samples primary samples from MLL-partial tandem duplication (MLL-PTD) acute myeloid leukemia (AML) patients. (B) Scatter plots showing changes in BRD4 binding peak scores upon JQ1 treatment in healthy CB and MLL- PTD AML samples. (C) Schematic overview over the bioinformatic approach used to identify the genes deregulated by BRD4 in MLL-PTD cells. A peak and gene pair was classified as MLL-PTD specific positive response when peak score and gene expression were in first quartile (0-25%) for CB samples, peak score and gene expression were in the top quartile (75-100%) for MLL-PTD dimethyl sulfoxide (DMSO) sample, and a decreased expression was observed in both peak score and gene expression for MLL-PTD sample upon JQ1 treatment (25% or more). Similarly, we identified potential oncosuppressor genes downregulated by MLL-PTD but restored by JQ1 treatment. Genes whose expressions were positively or negatively correlated with changes in BRD4 binding with at least 25% change under JQ1 treatment are shown in the Online Supplementary Table S1.(D) Heat map of genes that were found to be deregulated in MLL-PTD cells and which also showed a response to JQ1 treatment. (E) Example of one of 130 genes that fulfilled all criteria. ADAMDEC1 expression is increased in MLL-PTD AML cells by a binding of BRD4, and is downregulated upon JQ1 treatment.
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