Figure 5. sPrdm16 expression in HSCs shortens latency of MLL-AF9 leukemia.

(A) Survival of lethally irradiated mice transplanted with BM HSC-derived MLL-AF9 cells from Vav-Cre^–/– Prdm16^fl/fl (WT) and Vav-Cre^+/– Prdm16^fl/fl (KO) mice. (B) Colony-forming assays of MLL-AF9 cells from A (n = 4 independent assays in duplicate). (C) Survival of lethally irradiated mice transplanted with Prdm16^+/+ (WT), Prdm16^+/– (HET), or Prdm16^–/– (KO) FL HSC-derived MLL-AF9 cells. (D) Colony-forming assays of MLL-AF9 cells from C (n = 4 independent assays in duplicate). (E) Survival of lethally irradiated mice transplanted with MLL-AF9 cells generated from BM Lin^–Sca1^–Kit⁺ cells from Vav-Cre^–/– Prdm16^fl/fl (WT) and Vav-Cre^+/– Prdm16^fl/fl (KO) mice. (F) Survival of lethally irradiated mice transplanted with FL HSC-derived MLL-AF9 cells from Δ47-fPrdm16^–/– (KO) or WT littermate mice. (G) Expression of Prdm16 relative to HSC controls in stem and progenitor cells and in MLL-AF9 leukemic cells (n = 3, in triplicate). MPP, multipotent progenitor. (H) GO pathways significantly up- or downregulated in KO relative to WT MLL-AF9 cells from A. Values expressed as –log₁₀ of the P value, determined by PANTHER analysis. Mean ± SEM. NS, P > 0.05; 1-way ANOVA for multiple comparisons, Gehan-Breslow-Wilcoxon test for comparison of survival curves; n = 13–15 recipients from 3 independently derived MLL-AF9 lines for each of the survival experiments in A, C, E, and F.