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Fig. 1 | Molecular Cancer

Fig. 1

From: PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma

Fig. 1

PDGFRβ is a biomarker for aggressive ALCL. A Tissue microarrays from 98 NPM-ALK+ ALCL patients enrolled to NHL-BFM 90 and 95 studies and the ALCL99 clinical trial, were stained for total PDGFRβ by immunohistochemistry (IHC) and expression levels were correlated with event-free survival (EFS). Staining was quantified according to high (n = 11; orange line) versus low (n = 87; grey line) PDGFRβ expression. B PDGFRB and PDGFRA mRNA transcript levels (log2 median-centered intensity) comparison between (n = 6) ALCL patients and (n = 10, T cells; n = 5, CD4+; and n = 5, CD8+) healthy donors of the Piccaluga dataset [32] extrapolated from the Oncomine database. C Schematic representation of the breeding strategy to obtain a genetic knockout of Pdgfrb in CD4+ T cells harboring the human NPM-ALK+ oncogenic fusion under the control of the Cd4 enhancer. NPM-ALKTg littermates either expressing wild type Pdgfrb (fl/fl Pdgfrb; grey mouse) or lacking Pdgfrb in CD4+ T cells (Δ/Δ Pdgfrb; orange mouse) were generated using Cre-mediated recombination driven by the Cd4 promoter. D Representative pictures of PDGFRβ IHC analysis of fl/fl Pdgfrb and Δ/Δ Pdgfrb mouse thymomas at the experimental end point. Black squares in the left picture represent the area chosen for the magnification depicted on the right. Scale bars: 50 μm. Staining of (n = 6) end point thymic tumors per genotype were scanned and whole-slide quantification was performed using Definiens™ software. E Kaplan Meier cumulative survival analysis of (n = 3) wild type (black line), (n = 19) fl/fl Pdgfrb (grey line) and (n = 24) Δ/Δ Pdgfrb (orange line) mice in biological replicates. Values next to the dotted lines on the x-axis indicate median life expectancy for each genotype. F Quantitative RT-qPCR of Pdgfrb mRNA transcripts from (n = 4) fl/fl Pdgfrb (grey) and (n = 4) Δ/Δ Pdgfrb (orange) primary tumor cell lines. Pdgfrb levels were normalized to 18S ribosomal RNA expression and depicted as fold-change over one fl/fl Pdgfrb biological replicate set to 1. G Hematoxilin and Eosin (H&E)-stained sections of tumor dissemination into the liver of two fl/fl Pdgfrb (grey) and Δ/Δ Pdgfrb (orange) mice at the experimental end point. The black dashed line represents malignant infiltration into secondary organs. Scale bars: 50 μm. A and E p values were determined by the log-rank (Mantel-Cox) test. B, D, F and G Data are shown as the means ± SD and p values were determined by the unpaired two-tailed Student’s t-test (ns = p > 0.05; * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001)

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