RNA-Seq analysis of T-ALL mouse samples and the effect of Miz1 POZ domain deletions on T-ALL expression profiles. Mus musculus

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease mainly affecting children. Relapse rates are high and toxic chemotherapies that block DNA replication and induce DNA damage cause health problems later in life, underlining the need for improved therapies. We show that ablation of the BTB/POZ domain factor Miz-1 significantly delays Notch1-induced T-ALL in mice through induction of p53-dependent cell death. Leukemic cells that still emerge in this system activate DNA replication and strand elongation pathways, which are those targeted by current chemotherapeutic drugs such as cytarabine. Acute Miz-1 ablation enhances the effect of cytarabine treatment and eliminates leukemic cells completely in some cases, suggesting that targeting Miz-1 could render current T-ALL chemotherapies more effective. Overall design: Mice expressing mutant Miz1 protein lacking the POZ domain as well as wild-type controls developped Notch induced T-ALL. The same experiments were carried out in a p53 null background. For each genotype, RNA-Seq was carried out in 2 mice.