Page 118 - Haematologica May 2020

B.Z. Carter et al.
samples expressed statistically significantly higher p53 (P=0.019) and, although non-significant, higher BAX pro- tein levels, and that p53 and BAX levels in the CML-CP samples were highly correlated (R2=0.58, P=0.002) (Figure 2B). Note among the seven CML-CP samples tested, sam- ple #6, that had the lowest levels of p53 and BAX, was a PB sample. All of the other samples were derived from BM. All the normal controls were derived from BM.
Bone marrow lineage-SCA-1+C-KIT+ cells from chronic myeloid leukemia mice are sensitive to BH3 peptide-induced apoptosis
Induction of apoptosis is one of the major functions of p53, which occurs primarily through transcriptional acti- vation of pro-apoptotic BCL-2 family proteins such as BAX and NOXA. Our previous study of the overexpres- sion of BCL-2 proteins20 and the present assessment of
A
B
Figure 3. Priming analysis of bone marrow (BM) cells from Tet-off chronic myeloid leukemia (CML) and Tet-on control mice to BH3 peptides. BM cells were treated with various BH3 peptides (PUMA, 10 mM; all others, 100 mM) for 2 hours and 15 minutes. CD45+ or lineage-SCA-1+C-KIT+ (LSK) cells were analyzed using flow cytom- etry after the cells were stained with JC-1 and priming was calculated for each peptide. Error bars indicate standard error of the mean. BM cells were collected from mice 3-4 weeks after tetracycline cessation (Tet-off) (n=6) or from age-matched controls (Tet-on) (n=5). (A) Results of CD45+ cells (n=6 for Tet-off and n=5 for Tet- on). (B) Results of LSK cells (n=5 for Tet-off and n=2 for Tet-on).
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