Figure 8. Zeb1 is downregulated in AML patient samples and acts as a tumor suppressor in MLL-AF9 and Meis1a/Hoxa9-driven AML.

(A–C) ZEB1 RMA–normalized expression from combined published data sets in (A) control and AML, (B) across FAB subtypes and, (C) karyotypes. (D) ZEB1 log₂ expression data in human HSPC and AML karyotypes. Data from BloodSpot. Error bars show mean ± SEM. Student’s t test was used unless otherwise indicated. ****P < 0.0001. (E) C-KIT⁺ cells from control and Zeb1^fl/fl;Mx1-Cre⁺ mice were transduced with retroviruses expressing MLL-AF9 or Meis1a/Hoxa9 oncogenes and plated into CFC assays. After CFC3 (6 days each CFC), pre-LSCs (CD45.2⁺C-KIT⁺) were sorted and transplanted into lethally irradiated recipients together with CD45.1⁺ unfractionated BM cells. Three weeks later, mice were administered pIpC to induce gene deletion and monitored for AML development. (F and G) Kaplan-Meier survival curve of primary recipients transplanted with (F) MLL-AF9 (n = 4) or (G) Meis1a/Hoxa9 (n = 4) pre-LSCs. Mantel-Cox test. *P < 0.05.