Intrinsic suppression of IFN-I production and response in B-ALL predicts poor clinical outcome. (A)Comparison of relapse-free survival probabilities of COG P9906 B-ALL patients separated into two groups that is, IFNAR1HighIFNAR2HighSTAT1HighOAS1HighMX1High (‘High IFN-I Response’, n=15) and IFNAR1LowIFNAR2LowSTAT1LowOAS1LowMX1Low (‘Low IFN-I Response’ n=14) based on the median transcript expression of these genes. (B)Stacked bar charts comparing the proportions of COG P9906 B-ALL patients with WBC counts ≥100,000/μL or WBC counts <100,000/μL within the ‘High IFN-I Response’ and ‘Low IFN-I Response’ cohorts. (C)Comparison of IRF7 and CD123 transcript levels within the ‘High IFN-I Response’ and ‘Low IFN-I Response’ cohorts. (D–F)Comparison of IFNα2b+ cells in class C CpG ODN-stimulated total BMMCs (D), total PBMCs (E), and within the HLA-DR+ non-B, non-monocytes, non-T, and non-NK immune cell fraction of PBMCs (F)between B-ALL patients (n=7 BMMC, n=10 PMBC) and healthy donors (n=7 BMMC, n=10 PMBC) by flow cytometry. (G)Comparison of peripheral blood pDC frequencies within the HLA-DR+ non-B, non-monocytes, non-T, and non-NK immune cell fractions between B-ALL patients (n=10) and healthy donors (n=10) by flow cytometry. (H)Median fluorescence intensity (MFI) of CXCR4 expression on peripheral blood pDCs of B-ALL patients (n=7) and healthy donors (n=10) by flow cytometry. (I)MFI of HLA-DR expression on peripheral blood cDC of B-ALL patients (n=10) and healthy donors (n=10). (J)Analysis of frequencies of CD4+ and CD8+ T cells within non-leukemic pan T-cell fraction of B-ALL patients (n=6) and healthy donors (n=10) using mass cytometry. For all flow cytometry experiments, one representative histogram or dot plot from each group is shown. Survival was calculated by Kaplan-Meier method and p value calculated by log-rank test. All other comparisons between any two groups were conducted using Mann-Whitney U test. Exact p values are provided whenever significant. B-ALL, B-cell acute lymphoblastic leukemia; BMMC, bone marrow mononuclear cell; cDC, conventional dendritic cell; PBMC, peripheral blood mononuclear cell; pDC, plasmacytoid DC; WBC, white blood cell.