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Fig. 1 | Molecular Cancer

Fig. 1

From: Loss of FBXW7-mediated degradation of BRAF elicits resistance to BET inhibitors in adult T cell leukemia cells

Fig. 1

Activation of the MYC pathway in ATL patients. a MYC RT profiler arrays were performed on normal, non-HTLV-I infected, PBMCs and 7 PBMCs from uncultured, ATL patients’ samples. The top 20 up-regulated and down-regulated genes, compared to PBMCs, are highlighted. Fold change is compared to PBMCs. ATL patients, ATL2 (m425), ATL3 (m462), and ATL4 (m468) have mutations in FBXW7. ATL1 is wild-type FBXW7. b c-MYC and NMYC are highly expressed in ATL patients. Real-time PCR analysis of c-MYC and NMYC expression in ATL patients (n = 57) were performed in duplicates. Fold change is compared to normal PBMCs and patient samples are normalized to GAPDH expression. c c-MYC and NMYC do not significantly correlate with HTLV-I viral genes. Real-time PCR expression was determined for Tax, HBZ, c-MYC, and NMYC in uncultured ATL patients’ samples. Samples were normalized to GAPDH expression. Gene expression values of Tax and HBZ were plotted against gene expression values of c-MYC and NMYC. Correlations between MYC genes and Tax/HBZ were determined by Pearson Correlation Coefficient. p-values are indicated. d In vivo inhibition of MYC activity inhibits ATL cell tumor growth in a mouse xenograph model. MT1 cells stably transfected with a TET-inducible FBXW7 expression vector were injected into BALB/c-nu/nu mice. The mice were randomized into two groups after the tumors reached a mean volume of about 50 mm3, and then treated with vehicle or BET inhibitor JQ1. After 4 weeks tumors were surgically excised, weighed, and photographed. e The body weight was measured every 3 days. * is P value of < 0.05. f Tumors volume and tumors weight were measured in JQ1 treated animals and compared to controls. * is P value of < 0.05

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