MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

In this study, we identify MBNL1 as a unique molecular vulnerability across MLL-rearranged leukemias. Through transcriptomic profiling and novel splicing analyses of MLL-rearranged leukemia cell lines following shRNA knockdown of MBNL1, we show that MBNL1 regulates alternative splicing (predominantly intron retention) of genes essential to MLL-rearranged leukemogenesis, such as DOT1L and SETD1A. Overall design: Identification of MBNL1-dependent alternative splicing in MLL-fusion leukemia by RNAseq of MOLM-13 cells