The resistant aspect of Evi1-high cells to nilotinib would fit into clinical data that high EVI1 is related to TKI resistance.17 The in vivo quiescent status of Evi1-high CML-CP cells, which could proliferate aggressively in vitro, may be controlled by hypoxic BM niche microenvironment.50,51 In line with less dependence of CML stem cells on BCR–ABL,2,52,53 Evi1-high CML-CP LSK cells showed a comparable BCR–ABL to their Evi1-low counterpart, reflecting little addiction to BCR–ABL (Figure 2d). This evidence concerns the gene RUNX1 and chronic myelogenous leukemia, BCR-ABL1 positive.