Cancer Cell 2017 07;32(1):1-3
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
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Cancer Cell 2017 07 15;32(1):27-41.e4. Epub 2017 Jun 15.
Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2155c, 269 Campus Drive, Stanford, CA 94305-5168, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:
Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4 T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Read More
Future Med Chem 2012 Mar;4(4):471-86
Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Epigenetic modification by small-molecule histone deacetylase inhibitors (HDAC-Is) has been a promising new antineoplastic approach for various solid and hematological malignancies, particularly for cutaneous T-cell lymphoma (CTCL). Vorinostat, a pan-HDAC-I and, most recently, romidepsin, a bicyclic pan-HDAC-I, have been US FDA approved for treatment of relapsed or refractory CTCL. However, because many patients do not reach the 50% partial response mark and response is not always sustainable, overcoming HDAC-I resistance by adding other agents or finding more selective molecules is an important clinical problem in realizing the full clinical potential of HDAC-Is. Read More
PLoS One 2013 22;8(7):e68915. Epub 2013 Jul 22.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Given the fundamental roles of histone deacetylases (HDACs) in the regulation of DNA repair, replication, transcription and chromatin structure, it is fitting that therapies targeting HDAC activities are now being explored as anti-cancer agents. In fact, two histone deacetylase inhibitors (HDIs), SAHA and Depsipeptide, are FDA approved for single-agent treatment of refractory cutaneous T cell lymphoma (CTCL). An important target of these HDIs, histone deacetylase 3 (HDAC3), regulates processes such as DNA repair, metabolism, and tumorigenesis through the regulation of chromatin structure and gene expression. Read More
Cancer Discov 2016 09 15;6(9):986-1005. Epub 2016 Jul 15.
Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio. Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Unlabelled: Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15 Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Read More