JQ1 reverses BRD4 binding–mediated enhanced oncogene expression in vivo. (A) Gene tracks depicting genomic occupancy of BRD4 (rpm per bp) at regulatory regions of NOTCH1 and RBPJ in CD4+ T cells from a normal donor, a CTCL patient, and patient cells treated with 100 nM JQ1 for 24 hours in vitro. (B) RT-PCR of transcript levels of NOTCH1 and RPBJ in peripheral blood CD4+ T cells from normal donors (n = 6) and CTCL patients (n = 9). (C) Clinical images of representative IL-15 transgenic FVB/N mice treated intraperitoneally with 10% cyclodextran vehicle (above) or 50 mg/kg JQ1 (below) for 4 weeks. (D) Photomicrographs of skin from representative IL-15 transgenic CTCL mice treated with vehicle or JQ1. Hematoxylin and eosin stain, 40× (left), 400× (right). (E) Histology lesion severity score of skin tissue from mice treated with vehicle (n = 5) or JQ1 (n = 7). (F) Immunoblot of BRD4, NOTCH1, and RBPJ from skin tissue of IL-15 transgenic CTCL mice treated with vehicle or 50 mg/kg JQ1 with actin as an internal control. (G) Photomicrographs of skin from representative IL-15 transgenic mice treated with vehicle or JQ1. Immunohistochemistry for mouse CD3 (40×, left; 400×, right) and immunohistochemistry for mouse CD4 (40×, left; 400×, right). (H) Counts of CD3+ cells within surface and follicular epithelium (left) and within the superficial dermis (right) in vehicle-treated and JQ1-treated mice. (I) Counts of CD4+ cells within surface and follicular epithelium (left) and within the superficial dermis (right) in vehicle-treated and JQ1-treated mice. (J) RT-PCR of BRD4, NOTCH1, and RBPJ transcript levels in CTCL cell line HuT-102 transfected with 0.15 nmol siRNA to BRD4 for 24 hours (left). RT-PCR of BRD4, NOTCH1, and RBPJ transcript levels in CTCL patient CD4+ T cells transfected with 0.15 nmol siRNA to BRD4 for 24 hours (right). Data are presented as mean ± SEM unless otherwise specified. *P ≤ .05; **P ≤ .01; ***P ≤ .001; ****P ≤ .0001; unpaired 2-tailed Student t test.