Figure 6.

ALDH1A1⁻ acute myeloid leukemias (AMLs) are sensitive to 4HC+ATO while normal HSCs are relatively resistant. (A) 4HC+ATO in vitro treatment eliminated engraftment of primary AMLs in NSGS mice. Representative flow cytometric analysis of harvested bone marrow of Aldefluor^[0–0.1%] AMLs that underwent overnight ex vivo treatment with 4HC⁺ATO (30 μM+ 5 μM) or vehicle (left panels) and summary of xenotransplant data from the 3 AMLs treated in vitro and transplanted into NSGS mice (right panels). The data are a summary of 25 of 30 control and 25 of 30 treated mice analyzed after 12 weeks (**P<0.0005). (B) In contrast, 4HC+ATO in vitro treatment did not completely eliminate engraftment of normal CD34⁺UCB cells in NSGS mice. NSGS mice transplanted with 2 pooled UCBs following 4HC+ATO or vehicle treatment as above (treated: n=12; untreated: n=10). While level of engraftment was reduced, in contrast to the AML experiments above, 7 of 12 mice treated with normal CD34⁺UCB cells displayed more than 1% engraftment (*P<0.005). Analysis of engraftment in bone marrow was performed at 13 weeks using flow cytometry.