Figure 7.
Two CXCL chemokines and osteopontin/Spp1 are involved in the pathogenesis of MDS/MPN-like disease in 9p21+/− mice. (A) Cxcl13 protein level in mice serum was measured via enzyme-linked immunosorbent assay (ELISA). Symbols represent individual mice (WT mice, n = 23; 9p21+/− tumor mice, n = 27). (B) Cxcl13 protein level in mice serum was measured via ELISA at different time points of tumorigenesis. Symbols represent individual mice (WT mice, n = 3; 9p21+/− mice, n = 3). (C) Osteopontin protein level in mice serum was measured via ELISA. Symbols represent individual mice (WT mice, n = 22; 9p21+/− tumor mice, n = 25). (D) Osteopontin protein level in mice serum was measured via ELISA at different time points of tumorigenesis. Symbols represent individual mice (WT mice, n = 3; 9p21+/− mice, n = 3). (E) Cxcl12 protein level in mice serum was measured via ELISA. Symbols represent individual mice (WT mice, n = 27; 9p21+/− tumor mice, n = 36). (F) Cxcl12 protein level in mice serum was measured by ELISA at different time points of tumorigenesis. Symbols represent individual mice (WT mice, n = 3; 9p21+/− mice, n = 3). (G) Immunohistochemical staining of Cxcl12 in mice BM. The images represent individual mice. The results represent a total of 5 9p21+/− MDS/MPN mice and 6 WT mice. (H) Gene expression changes in the bone of patients with MDS. Symbols represent individual human samples. CXCL12 and CDKN2A (samples from healthy individuals, n = 5; samples from patients with MDS, n = 22); CXCL13 (samples from healthy individuals, n = 5; samples from patients with MDS, n = 17). RPKM, the reads per kilobase per million value. (I) Positive correlation between CXCL12 and CDKN2B in the bone of patients with MDS. Symbols represent individual patients with MDS (n = 22). Data represent the mean ± SD. Statistical significance was defined using Mann-Whitney test and is shown as ∗∗∗∗P < .0001 in panels A,C,E.