Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML)1, 2, 3. We have previously reported4 that CD34+CD38− human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rγnull mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.
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- Supplementary Text and Figures (9M)
Supplementary Figs. 1–5 and Supplementary Tables 1–5
- Supplementary Movie 1 (9M)
This movie shows a cross-sectional view through a three-dimensional reconstruction of the recipient femur shown in Fig. 2j. The bone section was labeled for human CD45 (red), Ki67 (green) and DAPI (blue). The serial cross-sectional images along the long axis of the bone demonstrate that there is little to no Ki67 expression by hCD45+DAPI+ AML cells in the BM endosteal region adjacent to the bone at baseline.
- Supplementary Movie 2 (8M)
This movie shows a cross-sectional view through a three-dimensional reconstruction of the recipient femur shown in Fig. 2k. The bone section was labeled for human CD45 (red), Ki67 (green) and DAPI (blue). The serial cross-sectional images along the long axis of the bone demonstrate the appearance of Ki67+hCD45+DAPI+ cells within the BM endosteal region following G-CSF treatment.