Figure 1

AML engraftment results in expansion of LT-HSCs, altered stromal compartments, reduced osteoblast number and bone architecture changes. (a) Neonatal DKO mice were injected with vehicle control or 2 million AML cells (MV411, KG1A, NB4 cell lines or COH101, COH103 patient samples) intrahepatically. The litter was killed when transplanted mice were moribund or 4 weeks after transplantation. Spleen weight of control and AML-transplanted (MV411, KG1A, COH101) DKO mice (n=5–7 mice per group in at least three independent experiments). (b) Frequency of the LT-HSC population in marrow of control and AML-transplanted (MV411, KG1A, NB4, COH101) DKO mice (n=5–8 mice per group in at least three independent experiments). (c) Frequency of Sca1+, CD146+ and CD166+ cells in the stromal compartment of control and AML-transplanted DKO mice (n=7–13 mice per group in at least three independent experiments). (d) Trichrome stain of bone sections from control and AML-transplanted (MV411, KG1A) DKO mice. Osteoblasts are marked with yellow arrows. (e) Immunofluorescence staining of bone sections from control or MLL-AF9-transplanted B6 mice. Staining of Sca1 and OCN (left) are shown. Osteoblasts are marked with yellow arrows. Number of Sca1+ cells in the view field determined by immunofluorescent staining (right). (f) Representative μ-CT 2D cross-section of trabecular bone region in femurs of control or AML-transplanted (KG1A, MV411) DKO mice. (g) Femurs of control or AML-transplanted (KG1A, MV411) DKO mice (n=6–8 in two independent experiments). Quantitative μ-CT analysis of cortical wall thickness in compact bone region, relative bone volume (BV/TV), thickness of trabecular bone, number of trabeculae and space between trabeculae in trabecular bone region. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.