Figure 2.
Cdc73 is important for Notch-induced T-ALL maintenance. (A) Experimental strategy to study dependence of Notch-induced T-ALL maintenance on Cdc73. (B-E) Mice were injected with 2 different primary ΔE/Notch1-induced Rosa26CreERT2 control T-ALL tumors (B,D) or 2 different primary ΔE/Notch1-induced Rosa26CreERT2Cdc73f/f murine T-ALL tumors (C,E). Numbers indicate tumor IDs. Peripheral blood green fluorescent protein–positive (GFP+) or white blood cell (WBC) counts for panels B-C at 2.5 weeks after transplant and survival for panels D-E were measured. (F) Western blot showing CDC73 knockdown in shRNA-transduced CEM cells. Numbers indicate relative band intensity. (G) Fold expansion (day 9 cell count / day 0 cell count) of Notch1-activated T-ALL cells transduced with 2 independent shCDC73. (H-I) Viability of conventional T-ALL PDX cells transduced with shCDC73 in OP9-DL4 stromal cell culture. N = 3. (J) Leukemia-free survival of NOD-scid-IL2γnull (NSG) mice injected with PDX4 cells transduced with shCDC73 that were passaged in NSG mice for 24 weeks. N = 5. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. cKO, comditional knockout; Tam, 25 mg/kg tamoxifen; WT, wild-type.