We aim to define the epigenetic landscape of iALLand identify the epigenetic changes that differentiate iALL cells from normal B cells, as well as MLL-r patients from MLL-wt patients. Using the same set of samples, we plan to explore the gene expression changes associated with this epigenetic dysregulation. To define the tumour-specific transcriptome, we will combine single-cell (sc)RNA-seq (BD Rhapsody single-cell analysis system)and small-RNA-seq to study the expression of protein-coding mRNAs and miRNAs, respectively. This strategy is likely to identify better suited targets for the treatment MLL-r versus MML-wt iALL, and to shed more light on the gene expression changes that healthy B cells undergo when transforming into iALL cells. Moreover, the BD®Rhapsody single-cell analysis systemwill allow for BCR sequencing, which will be instrumental to detect possible intra-tumoral clonal alterations of the iALL(i.e., clones harbouring stem cell features and possible derivatives from these). This will provide the possibility to identify biologically relevant differences in epigenetic signatures between multiple tumour clones in each iALL patient sample.