Figure 4.
Imetelstat is capable of eliminating MF SRCs. (A) Representative FACS plots showing hCD45 cell chimerism and hCD34+ cells detected in the marrow of NSG mice receiving the same MF splenic CD34+ cells treated with vehicle alone, MM, or Ime (15 mg/kg). (B-C) The absolute number of hCD45+ and hCD34+ cells generated in the marrow of NSG mice 4 months after the transplantation of MF splenic CD34+ cells. One week after the transplantation of MF splenic grafts, the recipient mice were treated with vehicle alone or both drugs, and the data were analyzed as described in Figure 3. n = 3. HCD45+ cells: P = .03, MM vs Ime. HCD34+ cells: P = .14, MM vs Ime. Data of 3 patient samples were pooled together and analyzed. Two independent experiments were performed for each patient sample. (D) The percentage of the absolute number of hCD45+ and hCD34+ cells detected in the marrow of secondary recipient mice receiving the BMCs harvested from primary recipient mice receiving Pt 5 splenic CD34+ cells treated with MM or Ime (15 mg/kg) relative to mice receiving same graft but treated with vehicle alone. (E) Absolute number of hCD45+ and hCD34+ cells generated in the marrow of the secondary recipient mice. Half of the BMCs collected from each primary recipient mouse receiving grafts from Pt5 were injected via the tail vein into a secondary recipient mouse and BMCs from the secondary recipient mouse were then harvested 2 months after the transplantation. Only BMCs from primary recipient mice transplanted with grafts from Pt5 that were treated alone with vehicle alone or MM but not imetelstat were able to reconstitute the secondary recipient NSG mice. BMCs, BM cells.