Interplay between the EMT transcription factors ZEB1 and ZEB2 regulates hematopoietic stem and progenitor cell differentiation and hematopoietic lineage fidelity
Fig 9
Inducible deletion of Zeb1/2 increases in vivo survival in MLL-AF9 secondary transplant settings.
(A) Schematic of inducible deletion strategy to investigate the effects of Zeb2 and Zeb1/2 deletion on secondary leukemia progression. (B) Tam-induced Zeb2 deletion was found to significantly increase overall survival of mice transplanted with MLL-AF9 secondary tumor cells compared to nontreated Veh treated controls (median survival 66 versus 42 days, p = 0.0082, Mantel–Cox test). There was a significant effect of Tam in Cre only treated samples compared to Veh controls (median survival 29 versus 19 days, p = 0.0082, Mantel–Cox test). (C) Tam-induced deletion of both Zeb1 and Zeb2 was also found to significantly increase overall survival of mice transplanted with MLL-AF9 secondary tumor cells compared to nontreated Veh treated controls (median survival 58 versus 31 days, p = 0.0031, Mantel–Cox test). There was a significant effect of Tam in Cre only treated samples compared to Veh controls (median survival 42 versus 31 days, p = 0042, Mantel–Cox test). N = 5 mice/treatment group for all arms of the experiments. Raw data behind graphs are included in F of S1 Data. BM, bone marrow; PB, peripheral blood; Tam, tamoxifen; Veh, vehicle.