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. Author manuscript; available in PMC: 2020 Sep 11.
Published in final edited form as: Leukemia. 2020 Feb 25;34(9):2460–2472. doi: 10.1038/s41375-020-0765-5

Figure 2. MDS Patients Exhibit Decreased Numbers of Dendritic Cell Committed Progenitors and Decreased Expression of IRF8.

Figure 2.

(A) Frequency of myeloid and erythroid colony-forming units (CFU) in MDS bone marrow specimens with low (CD141Hi cDCLow) or high numbers (CD141Hi cDCHigh) of CD141Hi cDCs as defined in Figure 1. For each group, n = 3 specimens from different patients. CFU assays were performed under normoxic and hypoxic (1% O2) conditions as described in Supplemental Methods. (B) Diagram depicting inverse relationship between multi-lineage potential (red triangle) and IRF8 expression (blue triangle) in specific hematopoietic stem and progenitor (HSPC) populations as defined by immunophenotype (described in the text). Intermediate stages in the differentiation of LMPPs and MLPs to DCs are shown as dotted lines. (C) Average frequency of different hematopoietic stem and progenitor (HSPC) populations in healthy donors (HD, black circles, n = 11) and MDS patients (red squares, n = 19). Monocyte-DC progenitors (MDP) and common DC progenitors (CDP) are displayed on a separate graph for clarity. Gating strategy and immunophenotypes are described in Supplemental Figure 1. p values were determined using the Mann Whitney t-test. (D) Correlations between numbers of MDPS and CDPs in HD (black circles) and MDS (red squares) bone marrow as determined using non-parametric Spearman’s rank-order correlation (r). (E) Average IRF8 expression as measured by flow cytometry in specific HD (black circles) and MDS (red squares) HSPC populations. (F) Average IRF8 expression in HD MDPs (n = 9, black circles) and in MDS MDPs separated based on IRF8 expression: IRF8Lo (< 2.0; n = 8, red circles); IRF8Hi (> 2.0; n = 10, blue circles). For (E) and (F), p values were obtained using unpaired t-test. (G) Average frequency of CDPs (Left) and CD141Hi cDCs (Right) in HD specimens and MDS specimens with IRF8Hi versus IRF8Lo MDPs. (H) Average frequency of CD141Hi cDCs in MDS specimens with IRF8Lo (n = 6) versus IRF8Hi (n = 6) CDPs. Patients were stratified based on median expression of IRF8 in MDS CDPs (IRF8Lo < 5.6, IRF8Hi > 5.6). Data are presented as values for individual patients. For (G) and (H), p values were determined using the Mann Whitney t-test. For all panels, horizontal bars represent the mean value and error bars represent standard error of the mean.