MHC-II and CIITA are selectively downregulated in CML stem/progenitor cells. (A) Ingenuity’s antigen presentation pathway overlaid with deregulation in CML vs normal G₀ CD34⁺ cells (n = 5 CML, n = 2 non-CML). Deregulated members for MHC II-α and II-β (including HLA-DP, DQ, DR) are shown expanded in the bottom left. Significantly downregulated components highlighted in green. (B) GSEA analysis demonstrating significant (false discovery rate [FDR], ≤0.15) downregulation of the extended MHC-II gene family in a larger, complementary microarray data set of G₀/quiescent (left) and dividing (right) CML and normal cells.¹⁴  (C) Heat map showing deregulation (as represented by logFC; see color scale below heat map) of the MHC-II gene family across multiple CML populations compared with corresponding non-CML cells from distinct microarray data sets, as indicated.^14,15  The data derived from the original data set¹³  is highlighted by the orange bar above the corresponding columns. Average normalized MFI of surface MHC-II expression in primary (D) CD34⁺CD38⁺ CML and non-CML stem/progenitor cells or (E) CD34⁺CD38⁻ CML LSCs and non-CML HSCs cultured for 48 hours in the presence or absence (UT) of IFN-γ (100 U/mL; n = 6 for CD34⁺CD38⁺; n = 4 for LSC; ± SEM). CD34⁺CD38⁻ cells, when stringently gated, represent ∼1% to 5% of bulk CD34⁺ cells and overlap considerably with either Hst^lo/Py^lo or CD34⁺ CFSE^max populations described previously.¹³  (F) Average gene expression of CIITA in bulk CD34⁺ CML and non-CML stem/progenitor cells cultured for 48 hours ± IFN-γ (mean fold change; n = 6; ± SEM). Statistical significance was calculated between UT CML sample and all other samples, and if significant, it is indicated by asterisks above the bars. Additional comparisons between samples are indicated by lines.