{"doi":"10.1038/s41598-021-87890-9","title":"Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia","abstract":"T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogenesis. We hypothesize epigenetic mechanisms also play a key role in T-PLL pathogenesis. To systematically test this hypothesis, we generated genome-wide maps of regulatory regions using H3K4me3 and H3K27ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals. We found that genes down-regulated in T-PLL are mainly associated with defense response, immune system or adaptive immune response, while up-regulated genes are enriched in developmental process, as well as WNT signaling pathway with crucial roles in cell fate decision. In particular, our analysis revealed a global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for binding motifs of immune related transcription factors, supporting the epigenetic regulation of oncogenes and genes involved in DNA damage response and T-cell activation. Together, our work reveals a causal role of epigenetic dysregulation in T-PLL.","journal":"Scientific Reports","year":2021,"id":209379,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":643085,"name":"Henan Zhang","orcid":"0000-0002-5680-4687","position":1,"is_corresponding":false},{"id":21512,"name":"Pan Zhang","orcid":"0000-0002-2233-9019","position":2,"is_corresponding":false},{"id":674746,"name":"Michael T. Kalmbach","orcid":null,"position":3,"is_corresponding":false},{"id":70826,"name":"Jeong‐Heon Lee","orcid":"0000-0003-4007-9166","position":4,"is_corresponding":false},{"id":70829,"name":"Tamás Ördög","orcid":"0000-0002-3940-7284","position":5,"is_corresponding":false},{"id":796989,"name":"Paul J. Hampel","orcid":"0000-0003-1292-3024","position":6,"is_corresponding":false},{"id":454796,"name":"Timothy G. Call","orcid":"0000-0002-8465-9587","position":7,"is_corresponding":false},{"id":11125,"name":"Thomas E. Witzig","orcid":"0000-0002-4215-6500","position":8,"is_corresponding":false},{"id":451444,"name":"Neil E. Kay","orcid":"0000-0002-5951-5055","position":9,"is_corresponding":false},{"id":242575,"name":"Eric W. Klee","orcid":"0000-0003-2946-5795","position":10,"is_corresponding":false},{"id":264807,"name":"Susan L. Slager","orcid":"0000-0002-5173-4712","position":11,"is_corresponding":false},{"id":323363,"name":"Huihuang Yan","orcid":"0000-0003-0756-2922","position":12,"is_corresponding":false},{"id":454795,"name":"Wei Ding","orcid":"0000-0001-9811-4601","position":13,"is_corresponding":false},{"id":451442,"name":"Shulan Tian","orcid":"0000-0002-3348-7439","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:05.171356Z","pmid":"33859327","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}