FIGURE 4.

Inhibition of miR‐126 increases human MDS cell cycling and sensitizes cells to DAC treatment. A‐D. Relative miR‐126 expression levels (A), cell cycling, as indicated by Ki‐67 staining (B), apoptosis, as indicated by Annexin V staining, (C) and colony‐forming cell (CFC) (D) in primary MDS CD34⁺ cells exposed to miRisten or SCR. (E and F) Apoptosis, as indicated by Annexin V staining (E), and viability, as measured by luminescence assays (F), in primary MDS CD34⁺ cells exposed 72 h to SCR, miRisten, DAC or a miRisten/DAC combination. G. Experimental design used to establish MDS patient‐derived xenografts. NSGS mice were transplanted with MDS CD34⁺ cells after cells were treated ex vivo with SCR, miRisten, DAC, or the miRisten/DAC combination for 72 h. BM, PB, and SP cells were then harvested and analyzed. H‐J: hCD45⁺ cell engraftment in BM (H), PB (I), and SP (J) in NSGS mice treated with SCR, single drug, or the miRisten/DAC combination at 12 weeks post‐BMT (n = 4‐5 per group). Results shown represent mean± SEM. *P < 0.05, **P < 0.01, ***P < 0.001,****P < 0.0001; NS, not significant; by two‐tailed, paired Student's t‐test