Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer 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. c-Myc is a transcription factor that is hyperactive in a large proportion of cancers including leukemia but is difficult to target in therapy. We show that ablation of the function of the BTB/POZ domain factor Miz-1, an important co-factor of c-Myc, significantly delays T- and B-ALL/lymphoma in mice and interferes with c-Myc oncogenic transcriptional activity. Leukemic cells that still emerge in this system activate DNA replication pathways, which are those targeted by current chemotherapeutic drugs such as cytarabine. We found that the combination of acute ablation of the Miz-1 POZ domain enhances the effect of cytarabine treatment. This combination was effective in both E-Myc and Notch ICN driven leukemia models and prolonged survival of tumor bearing animals by accelerating apoptosis of leukemic cells. These observations suggest that targeting Miz-1 could render current ALL chemotherapies more effective with a better outcome for patients. SOURCE: Möröy Tarik (tarik.moroy@ircm.qc.ca) -  Insititut de Recherches Cliniques

Pluto Bioinformatics

GSE120001: Effect of Miz1 POZ domain deletion on expression profiles of B and T leukemia cells