@article{f5471ca0c1a34e6da7a1dfb87374b8c8,
title = "Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors",
abstract = "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. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy. Qu et al. show that the accessible chromatin landscape distinguishes leukemic from host T cells in cutaneous T cell lymphoma (CTCL) patients as well as T cells from healthy individuals. The clinical response of CTCL to HDAC inhibitors strongly associates with a concurrent gain in chromatin accessibility.",
keywords = "CTCL, HDAC inhibitor, cancer epigenetics, response predictor",
author = "Kun Qu and Zaba, {Lisa C.} and Satpathy, {Ansuman T.} and Giresi, {Paul G.} and Rui Li and Yonghao Jin and Randall Armstrong and Chen Jin and Nathalie Schmitt and Ziba Rahbar and Hideki Ueno and Greenleaf, {William J.} and Kim, {Youn H.} and Chang, {Howard Y.}",
note = "Funding Information: We thank members of Chang and Greenleaf labs for discussions, Grant Ognibene and Illisha Rajasansi for coordinating and collecting patient samples, and all the patients for participation. This work was supported by Haas Family Foundation (to Y.H. and H.Y.C.), NIH grant P50-HG007735 (to. H.Y.C. and W.J.G.), R35-CA209919 (to H.Y.C.), Stanford Cancer Institute (to Y.H. and H.Y.C.), the National Natural Science Foundation of China grant 91640113 (to K.Q.), the Chinese Government 1000 Youth Talent Program (to K.Q.), the research start-up from the University of Science and Technology of China (to K.Q.). H.Y.C. is a scientific co-founder of Epinomics and a member of its scientific advisory board. W.G.J. is a scientific co-founder of Epinomics and a member of its scientific advisory board. P.G.G. is a co-founder and employee of Epinomics. H.Y.C. is a member researcher of the Parker Institute for Cancer Immunotherapy. We thank the Supercomputing Center of the University of Science and Technology of China for providing supercomputing resources for this project. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jul,
day = "10",
doi = "10.1016/j.ccell.2017.05.008",
language = "English (US)",
volume = "32",
pages = "27--41.e4",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}