Figure 3
Evi1-high CML-CP cells show CML engraftment capacity and TKI resistance in vivo. (a) Design of non-competitive repopulation assay with Evi1-high or Evi1-low LSK cells from Evi1+/GFP BCR–ABLtg/− mice. (b) Representative FCM data of PB from recipients 16 weeks after BMT were shown to distinguish donor cells (CD45.2+CD45.1–) from recipient cells (CD45.2-CD45.1+). (c) Serial assessments of PB from recipients as for donor chimerism were done every 4 weeks after BMT (n=8 mice per group). (d) Kaplan–Meier plot of the survival of recipient mice transplanted with 5000 Evi1-high or Evi1-low LSK cells from Evi1+/GFP BCR–ABLtg/− mice (n=6 mice per group, P=0.0183). (e) Vehicle or nilotinib (75 mg/kg daily) were administered orally to Evi1+/GFP BCR–ABLtg/− mice for a week just after the CML development and the number of the residual LSK cells in femur were calculated (CML: with vehicle; CML nilo: with nilotinib; n=6 mice per group). (f) Schematic abstract of Evi1 knock-out CML transgenic mice. Evi1+/+ or Evi1+/− mice were crossed with BCR–ABLtg/− mice to generate Evi1+/+ BCR–ABLtg/− or Evi1+/− BCR–ABLtg/− mice. (g) Kaplan–Meier plot of the survival of Evi1+/− BCR–ABLtg/− or Evi1+/+ BCR–ABLtg/− mice (n=7 for Evi1+/− BCR–ABLtg/− mice and n=14 for Evi1+/+ BCR–ABLtg/− mice, P=0.0106). Data are mean±s.d. +P<0.05, *P<0.01, ***P<0.0001.
