Figure 6.
2-Deoxyglucose preferentially targets Calr mutant cells in a preclinical MPN mouse model. (A) Schematic overview of chimeric transplantation experiment. CD45.1+ competitor BM cells were mixed in a 1:1 ratio with CD45.2+CalrΔ52/+ MxCre UBC-GFP BM and transplanted into lethally irradiated CD45.1+ recipient animals. N = 5 to 7 mice per group. (B-D) Peripheral blood values of engrafted and pI:pC-induced vehicle or 2-DG–treated chimeric mice as described in (A). (B) Platelet (PLT) count over time. (C) WBC over time. (D) GFP chimerism in peripheral blood platelets over time. (E) CalrΔ52/+ mutant chimerism (percentage of GFP+ cells) in long-term hematopoietic stem and progenitor cells in the bone marrow following 6 weeks of treatment. Statistical significance was determined using Skidak’s multiple comparisons tests (B-D) or 2-sided Student t tests (E). Mean plus or minus standard error of the mean. **P < .01. CBC, complete blood cell count; LT-HSC, long-term hematopoietic stem cell.