Fig. 13

MAKV-8-imatinib combination reduces cancer stem cell population. CML cells were treated with the indicated concentrations of imatinib alone or in combination with MAKV-8. (a) Boxplots illustrating fold-change (log2) of c-MYC mRNA expression in CD34+CD38- stem cells isolated from healthy (n=7) and CML (n=11) patients (represented by triangles). (b) Analysis of aldehyde dehydrogenase (ALDH) activity in K-562 cells cultured for 24h and known to present a substantial proportion of cells with cancer stem-like characteristics. Elevated ALDH activity is an established marker for the identification of hematopoietic stem cells. The ALDH inhibitor diethylaminobenzaldehyde (DEAB) was used to distinguish cell subpopulations with low and high ALDH activity. Representative dot plots where the percentage of ALDH+ cells is indicated (upper panel) and corresponding quantifications (lower panel) representative of three independent experiments are presented. SAHA was used as a reference HDACi. (c) K-562 cells were treated for 24h, fluorescently labeled, and then injected into the zebrafish yolk sac. Three days post-injection, pictures of 5 to 8 fishes (one representative set of pictures is presented) were taken, and the fluorescence intensity was quantified