IKAROS represses WDR5 transcription in T-ALL. (A-B) Effect of IKZF1 KD on WDR5 expression in mRNA level by quantitative polymerase chain reaction (qPCR; A) and protein level in CEM and MOLT4 cells (B). (C) Effect of IKZF1 overexpression on WDR5 protein level in CEM (left) and MOLT4 (right) cells. (D) Effect of IKAROS on the activity of the WDR5 promoter assessed by luciferase reporter assay in 293T cells. (E) Effect of CX-4945 on IKAROS binding at the WDR5 promoter as measured by quantitative chromatin immunoprecipitation (qChIP) in CEM (left) and MOLT4 (right) cells. (F) The effect of IKZF1 KD on CX-4945–induced WDR5 expression change in mRNA level by qPCR in CEM (upper) and MOLT4 (lower) cells. (G) Schematic representation of the xenograft mice model. CEM-shNC or CEM-shWDR5 cells were IV injected into NCG mice and the following 4 groups of mice were established: group CEM-shNC plus vehicle (receive vehicle daily through gavage for 25 days); group CEM-shNC plus CX-4945 (receive CX-4945 daily through gavage at 100 mg/kg for 25 days); group CEM-shWDR5 plus vehicle (receive vehicle daily through gavage for 25 days); and group CEM-shWDR5 plus CX-4945 (receive CX-4945 daily through gavage at 100 mg/kg for 25 days). (H) Kaplan-Meier survival curves of 4 groups of mice. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.