Figure 2.
Nestin+ Cells Promote Leukemia Chemoresistance In Vivo
(A) Scheme showing the experimental setting to simultaneously study the impact of nestin+ cell depletion on healthy and leukemic hematopoietic cells. Lethally irradiated CD45.2 control mice or Nes-creERT2;iDTA mice were transplanted with 106 iAML (rtTA;MLL-AF9) CD45.2+ BM nucleated cells and 106 CD45.1+ WT BM nucleated cells. Doxycycline administration started 2 weeks after transplant; tamoxifen was administered 4 weeks post-transplant and mice were sacrificed and analyzed 4 weeks later.
(B–D) Number of WT and MLL-AF9+ WBC (B), spleen weight (C), BM nucleated, and lineage-negative cells (D).
(E) BM lin−ckitlosca1− (LKlo) cells. Data in (D and E) represent the cellularity of 4 limbs, sternum, and spine (n = 18 mice/group, pooled from 3 independent experiments).
(F–I) Nestin+ cells support chemoresistance in AML mice. (F) WBCs, (G) spleen weight, (H) BM nucleated cells, and (I) LKlo cells in control (iDTA−) or Nes-creERT2;iDTA (iDTA+) mice transplanted with a mixture of WT and iMLL-AF9 BM cells, receiving tamoxifen and AraC treatment simultaneously, as in Figure S1A (n = 4–8). Dots represent data from individual mice. Data are mean ± SEM. ∗p < 0.05; ∗∗∗p < 0.001; unpaired two-tailed t test.