Figure 4. Concurrent knockdown of MDA5 and ADAR1 rescues self-renewal to various degrees in different T-ALL models.

(A) Experimental setup. T-ALL CD34⁺ cells were transduced with shCTRL, shADAR1, or shADAR1 and shMDA5 lentivirus in combination. Transduced cells were sorted based on GFP⁺mCherry⁺ (GFP for shADAR1 and mCherry for shMDA5), and serial transplant potential was measured in recipient Rag2^−/−γc^−/− mice.

(B–D) Serial leukemia engraftment and representative bone marrow FACS plots of patient 070 (B), patient 081 (C), and patient 076 (D) were determined for shCTRL, shADAR1, and shADAR1 in combination with shMDA5 (3–8 mice per condition).

(E) Images of spleen (left) and spleen weights (right) in serial transplanted mice were determined after an 8 week engraftment interval (n = 3 mice per group).

*p < 0.05, **p < 0.01, and ***p < 0.001, unpaired Student’s t test.