Endogenous LIPG is critical for proliferation and chemo-resistance of liver resident leukemia cells.
A-B, Mice were transplanted with control or LIPG-KO bulk leukemia cells. One cohort of mice were treated with chemotherapy consisting of 5-day treatment of Ara-C (50 mg/kg, i.p.) and 3-day treatment of doxorubicin (1.5 mg/kg, i.p., first 3 days) starting day 8 after transplantation. The other cohort was untreated. Mice were sacrificed at day 13 after transplantation. Leukemic burden, leukemic cell number (per whole liver or per femur + tibia) and fold changed (A) and LSC percentage (B) in BM and liver were determined (n=4).
C, Phosphorylation of Erk in control and LIPG KO lin− leukemia cells.
D, LA level in control and LIPG KO lin− leukemia cells (n=3).
E, Survival of mice transplanted with control or LIPG KO leukemia cells (10,000 bulk leukemia cells / mouse) treated with or without chemotherapy (same regimen shown in Fig. 5A) (n=7).
F, Expression of anti-apoptotic proteins in control and LIPG KO lin− leukemia cells.
G, mRNA level of anti-apoptotic proteins in LIPG-OE, LIPG KO and control lin− leukemia cells. Error bars denote mean ± SD from triplicates.
H, LIPG-OE, LIPG KO and control lin− leukemia cells were treated with indicated doses of cycloheximide for indicated time periods. BCL-XL protein level was examined.
Error bars denote mean ± SD.*p<0.05 , **p<0.005, ***p<0.005.