Figure 3.
Pbrm1-deficient AML cells are less immunogenic, with attenuated IFN signaling and reduced MHC expression. (A) Volcano plot of RNA-seq data from mouse AML cells, comparing Pbrm1-intact and Pbrm1-deficient AML cells. Red dots denote MHC II–related genes. (B) GSEA showing IFN pathways, including IFN-⍺ and IFN-γ, and signaling pathways involved in IFN signaling (TNF-⍺) were significantly downregulated in Pbrm1-deficient AML cells (see supplemental Figure 4D-E for the full list). Normalized enrichment score (NES) and false discovery rate (FDR) are as indicated. (C) Experimental design for secondary transplantation into NSG mice (see “Material and methods” for details). (D) Kaplan-Meier survival analysis of secondary transplantation in NSG mice. n = 20 and 16 from 5 primary donors in each group; P = .4752. AML was modeled based on Tet2/Tet3 deletions in mice.