Inhibition of CHD4 sensitizes AML blasts to DNR and ara-C in a xenograft model. Equal numbers of luciferase-expressing Scramble and shCHD4 U937 cells were engrafted into NSG mice by tail-vein injection and tumor burden was noninvasively monitored by measuring the total radiance generated upon subcutaneous administration of luciferin. (A) Once a tumor was well established (as seen in the pretreatment panels), the mice were treated with 5 continuous days of ara-C, with concurrent doxorubicin on days 1 through 3. Posttreatment, mice engrafted with control cells were found to possess 43% of their pretreatment radiance, whereas mice engrafted with CHD4-depleted cells possessed 20% (P < .001). (B) The mice were followed for survival. CHD4 depletion alone resulted in a 7-day improvement in mouse survival. Treatment with Doxorubicin/ara-C improved the survival of the mice engrafted with CHD4-depleted cells by an additional 4 days. *P < .05.