Expression data from wild type, CBFB-MYH11-overexpressing, DNMT3A knockdown and RUNX1 knockdown K562 cells

We searched for genes which are mutated in a manner that is linked with gene mutations involved in DNA de/methylation in AML. We found that recurrent CBFB-MYH11 fusions, which result in the expression of fusion protein comprising core-binding factor ß (CBFB) and myosin heavy chain 11 (MYH11), occur mutually exclusively with DNMT3A mutations. The CBFB-MYH11 fusion tumors show DNA hypomethylation patterns similar to cancers with loss-of-function mutation of DNMT3A. Expression of CBFB-MYH11 fusion protein or inhibition of DNMT3A similarly impairs the methylation and expression of target genes of Runt related transcription factor 1 (RUNX1), a functional partner of CBFB. We demonstrate that RUNX1 directly interacts with DNMT3A and that CBFB-MYH11 fusion protein sequesters RUNX1 in the cytoplasm, thereby preventing RUNX1 from interacting with and recruiting DNMT3A to its target genes. Our results identify a novel regulation of DNA methylation and provide a molecular basis how CBFB-MYH11 fusion contributes to leukemogenesis. Overall design: mRNA profiles of overexpression of plvx-vector/flag-CBFB-MYH11 fusion protein in K562 cells. And mRNA profiles of Knockdown of DNMT3A/RUNX1 in K562 cells as well as control K562 cells(PLKO). Expression levels of genes as well as repetitive elements were investigated.