IDH1 and leukemia: Pre-clinical in vivo studies suggest that the synergy of AZA and IDH inhibitor combination is due to rapid depletion of leukaemia stem cells driven by: (1) the IDH-inhibitor induced up-regulation of gene networks required for HMA efficacy, including cell-cycling and pyrimidine salvage; and (2) the enhanced transcriptional response, including increased myeloid differentiation and self-renewal repression, induced by the combination relative to the single-agents [29,109].