Figure 1.
GW9662 inhibits Se-S protection in CML mice. Se-S mice were given daily i.p. injection of GW9662 (1 mg/kg) starting 1 day prior to BCR-ABL transplant, until euthanized. (A) CBC (K/μL blood), WBC, eosinophil (EO), monocyte (MO), neutrophil (NE) profile of Se-S BCR-ABL mice treated with or without GW9662 (n = 4). (B) Flow cytometry of peripheral blood GFP expressed as percentage of gated input in Se-S BCR-ABL transplanted mice (5 × 105 events collected, gated on forward scatter [FSC]) (n = 8). (C) Representative image and spleen weight of Se-S BCR-ABL mice treated with or without GW9662 (n = 11-12). (D) Flow cytometric analysis of GFP in the spleen (left) and bone marrow (right) of Se-S BCR-ABL mice treated with or without GW9662 (n = 6-8). Counts are shown. (E) LSC analysis by flow cytometry in the spleen (left) and bone marrow (right) of Se-S BCR-ABL mice treated with or without GW9662. Lin− cells were gated on the GFP+ population (shown in panel D). Total counts (GFP+Sca-1+c-Kit+) are shown. Gates are based on GFP control and fluorescence minus one controls (n = 5-8). (F) Lin− Se-S BCR-ABL splenocytes (2 × 104) were plated in technical triplicate in Methocult and counted on day 10. LSC-CFUs were counted and plotted as total counts (n = 8). (G) PPARγ inhibition with GW9662 in Lin− Se-S BCR-ABL splenocytes by qPCR (n = 4). In panels B through E, the dashed line represents untreated, Se-A BCR-ABL control. Bars represent average of each biological mean ± SEM. The Student 2-way t tests were performed to compare groups. Error bars represent biological mean ± SEM. *P < .05; **P < .01; #P < .0001.