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.
Original language | English (US) |
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Pages (from-to) | 27-41.e4 |
Journal | Cancer Cell |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - Jul 10 2017 |
Externally published | Yes |
Keywords
- CTCL
- HDAC inhibitor
- cancer epigenetics
- response predictor
ASJC Scopus subject areas
- Oncology
- Cancer Research