STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma
Year: 2024
Type: article
Abstract: T cell lymphoma of children and adults. ALK fusion transcripts or mutations in the JAK-STAT pathway are observed in most ALCL tumors, but the mechanisms underlying tumorigenesis are not fully understood. Here, we show that dysregulated STAT3 in ALCL cooccupies enhancers with master transcription factors BATF3, IRF4, and IKZF1 to form a core regulatory circuit that establishes and maintains the malignant cell state in ALCL. Critical downstream targets of this network in ALCL cells include the protooncogene MYC, which requires active STAT3 to facilitate high levels of MYC transcription. The core autoregulatory transcriptional circuitry activity is reinforced by MYC binding to the enhancer regions associated with STAT3 and each of the core regulatory transcription factors. Thus, activation of STAT3 provides the crucial link between aberrant tyrosine kinase signaling and the core transcriptional machinery that drives tumorigenesis and creates therapeutic vulnerabilities in ALCL.
Source: Cell Reports Medicine
Institutions: Boston Children's Hospital, Dana-Farber Cancer Institute, St. Jude Children's Research Hospital, Broad Institute, Harvard University, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Massachusetts Institute of Technology, University of Cambridge, Addenbrooke's Hospital, Masaryk University, Medical University of Vienna, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: Lymphoma Research Foundation, Alex's Lemonade Stand Foundation for Childhood Cancer, St. Baldrick's Foundation, St. Jude Children's Research Hospital, Charles A. King Trust, Barr Foundation, American Lebanese Syrian Associated Charities, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Cancer Research UK, European Commission, Austrian Science Fund, National Institutes of Health, National Cancer Institute
OpenAlex ID: W4393061038