LSD1 suppression by an shRNA approach led to a reduction of mouse MLL leukaemic stem cells (LSCs).48 Although this study suggests a requirement of H3K4 demethylase for MLL leukaemia, a recent report revealed an opposite role of H3K4 demethylase KDM5B that negatively regulated MLL LSC (Figure 1c).49 In this study, H3K4me2/3 but not H3K79me2 were critical for MLL LSC, and H3K4 methylation levels reduced during differentiation. The gene discussed is KDM5B; the disease is leukemia.