T-cell acute lymphoblastic leukemia (T-ALL) is a cancer that arises in normal blood cells and hijacks normal T-cell development pathways to cause a malignant disease. Normal T-cell development is well studied and the majority of genomic changes that occur in T-ALL are known. From these data, there is clear evidence that chromatin structure, transcription and translation are major processes that are deregulated in T-ALL, but how specific mutations cooperate to change chromatin, gene expression and protein translation remains poorly studied. In this project, we aim to deconvolute T-ALL development at single-cell resolution in accurate mouse models of T-ALL by mapping chromatin, transcriptional and protein changes from the early stages of leukemia initiation to the progression towards acute disease. Moreover, we aim to map the interactions of the developing leukemia cells with the normal cells and determine how transcriptional and/or translational inhibitors affect leukemia cell function.