Fig. 6: Hematopoietic stem and progenitor (HSPC) features of a Chek2 p.I161T mouse model. | Leukemia

Fig. 6: Hematopoietic stem and progenitor (HSPC) features of a Chek2 p.I161T mouse model.

From: Predisposition to hematopoietic malignancies by deleterious germline CHEK2 variants

Fig. 6

A Survival in Chek2wt/wt (blue, N = 13), Chek2p.I161T/wt (red, N = 16), vs. Chek2p.I161T/p.I161T (green, N = 11) mice. B Representative flow plots from lineage depleted marrow demonstrating the Lin-CD34+ and Lin-Sca1+cKit+ compartments in young (2-6 month) Chek2 wt (Chek2wt/wt), heterozygous (Chek2p.I161T/wt), and homozygous (Chek2p.I161T/p.I161T) mice. C Comparison of Lin-CD34+ compartment in young Chek2 mice. D Comparison of Lin-cKit+ compartment in young Chek2 mice. E Comparison of the Lin-Sca1+cKit+ compartment in young Chek2 mice. F Representative flow plots from whole bone marrow nucleated cells (BMNC) demonstrating the CD34+ and cKit+ in aged (24 month) Chek2 wt (Chek2wt/wt), heterozygous (Chek2p.I161T/wt), and homozygous (Chek2p.I161T/p.I161T) mice without pathologic evidence of malignancy. G Comparison of cKit+ compartment in aged Chek2 mice. H Comparison of CD34+ compartment in aged Chek2 mice. I Pre-ranked gene set enrichment analysis (GSEA) for differentially expressed genes from Lin-CD34+ cells from young (aged 5-6 month) Chek2 mice. Highlighted pathways are significant at a false discovery rate (FDR) of <0.25. Pathways from MSigDb m2.all gene set with some titles abbreviated. Full pathway titles and details are in Supplemental Table 7. J–L Summary of consensus diagnosis obtained by analysis of gross features, histology, IHC, and multicolor flow cytometry data from wt (Chek2wt/wt), heterozygous (Chek2p.I161T/wt), or homozygous (Chek2p.I161T/p.I161T) mice. M Comparison of mice with identified pathologic abnormalities at endpoint for Chek2-wt (left) vs. Chek2-mt (right), including heterozygous or homozygous mice. (ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001).

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