Figure 5
MLL-AF9 AML exhibits cell-intrinsic Wnt activation. (A) Wnt signaling is enhanced in AML caused by the MLL-AF9 fusion oncogene. A comparison of gene expression analysis was performed on CD34+ patient cells (n = 10, enriched for HSC activity) and leukemia cells from patients with MLL-AF9–associated AML (n = 20). Unsupervised hierarchical clustering analysis of differentially expressed genes between CD34+ and AML samples. (B) Genes overexpressed in CD34+ were associated with inhibition of Wnt pathway, whereas genes overexpressed in AML were associated with activation of Wnt pathway. (C) Western blot of MLL-AF9 AML whole bone marrow compared with WT control bone marrow. (D) Western blot of representative AML samples derived from WT or Dkk1 recipient mice showing no difference in β-catenin stabilization between WT or Dkk1 recipient. (E) Real-time quantitative PCR on RNA extracted from LSCs. Analysis of gene expression of candidate Wnt/β-catenin target genes Cyclin D1 (Ccnd1), cMyc, and Axin2. Ccnd1 expression was higher in Dkk1 recipients than WT controls (P = .02); however, there were no significant differences between expression of cMyc or Axin2. The expression of canonical Wnt targets Tcf7 and Lef1 was below the detection of the assay.

MLL-AF9 AML exhibits cell-intrinsic Wnt activation. (A) Wnt signaling is enhanced in AML caused by the MLL-AF9 fusion oncogene. A comparison of gene expression analysis was performed on CD34+ patient cells (n = 10, enriched for HSC activity) and leukemia cells from patients with MLL-AF9–associated AML (n = 20). Unsupervised hierarchical clustering analysis of differentially expressed genes between CD34+ and AML samples. (B) Genes overexpressed in CD34+ were associated with inhibition of Wnt pathway, whereas genes overexpressed in AML were associated with activation of Wnt pathway. (C) Western blot of MLL-AF9 AML whole bone marrow compared with WT control bone marrow. (D) Western blot of representative AML samples derived from WT or Dkk1 recipient mice showing no difference in β-catenin stabilization between WT or Dkk1 recipient. (E) Real-time quantitative PCR on RNA extracted from LSCs. Analysis of gene expression of candidate Wnt/β-catenin target genes Cyclin D1 (Ccnd1), cMyc, and Axin2. Ccnd1 expression was higher in Dkk1 recipients than WT controls (P = .02); however, there were no significant differences between expression of cMyc or Axin2. The expression of canonical Wnt targets Tcf7 and Lef1 was below the detection of the assay.

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