Fig. 5: Immune evasion in NPM1 class I and II.
From: The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes
a Average expression of genes encoding MHC class I (MHC-I) and II (MHC-II) components, non-classical HLA genes, and the MHC-II master regulator CIITA, based on 98,022 AML immature cells from 38 AML samples and 5958 hematopoietic stem cells (HSC) from three normal bone marrow (NBM) samples. b Expression of MHC class II genes in HSC cells from NBM-CD34 (n = 5958 cells) and NBM-MNC (n = 282 cells) and in AML immature cells from the subtypes NPM1 class I (n = 21,458 cells), NPM1 class II (n = 10,382 cells), AML-MR (n = 26,549 cells), TP53 (n = 12,142 cells), Other (n = 9565 cells), CBFB::MYH11 (n = 8026 cells), and RUNX1::RUNX1T1 (n = 9900 cells), based on single cell RNA-sequencing data. Box-and-whisker plots inside violin plots show median (center line), first and third quartiles (hinges), and 1.5x interquartile range (whiskers). The expression was significantly lower in AML immature cells from NPM1 class I samples compared to both HSC cells from NBM-CD34 (two-sided Mann-Whitney U test, P < 2.2e−16) and AML immature cells from NPM1 class II samples (two-sided Mann-Whitney U test, P < 2.2e−16). c Expression of HLA-DR, HLA-DP and HLA-DQ on the cell surface of CD34 + CD38– cells from NBM and AML immature cells from NPM1-mutated samples by flow cytometry. Gating of AML immature cells was based on markers determined by single-cell antibody-derived tag-sequencing (gating strategy described in Supplementary Figs. 21, 22). Left panel: the geometric mean fluorescence intensity (MFI) values were significantly lower for NPM1 class I samples (n = 11 samples) compared to both NPM1 class II (n = 8 samples; two-sided Mann-Whitney U test; P = 0.00003) and NBM (n = 4 samples; two-sided Mann-Whitney U test; P = 0.0372). Right panel: histograms for AML immature cells from representative samples for each group and CD34 + CD38– cells from NBM. d Survival of AML cells after three-day ex vivo coculture with allogeneic T cells. NPM1 class II AML cells (n = 6 samples) were significantly less sensitive to allogeneic T cells than NPM1 class I AML cells (n = 7 samples, two-sided Mann-Whitney U test, P = 0.014). Source data are provided as a Source Data file.
