STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.

Autor:	Prutsch N; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA., He S; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA., Berezovskaya A; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA., Durbin AD; Division of Molecular Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Dharia NV; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02141, USA., Maher KA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Matthews JD; Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK., Hare L; Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Pediatric Oncology and Hematology, Addenbrooke's Hospital, Cambridge, UK., Turner SD; Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Faculty of Medicine, Masaryk University, Brno, Czech Republic., Stegmaier K; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02141, USA., Kenner L; Department of Pathology, Unit of Experimental and Laboratory Animal Pathology, Medical University of Vienna, Vienna, Austria., Merkel O; Department of Pathology, Unit of Experimental and Laboratory Animal Pathology, Medical University of Vienna, Vienna, Austria., Look AT; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: thomas_look@dfci.harvard.edu., Abraham BJ; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: brian.abraham@stjude.org., Zimmerman MW; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: mwz2002@gmail.com.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Mar 19; Vol. 5 (3), pp. 101472.
DOI:	10.1016/j.xcrm.2024.101472
Abstrakt:	Anaplastic large cell lymphoma (ALCL) is an aggressive, CD30 + 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. Competing Interests: Declaration of interests K.S. is a member of the scientific advisory board and has stock options in Auron Therapeutics and received grant funding from Novartis and KronosBio on topics unrelated to this paper. B.J.A. is a shareholder in Syros Pharmaceuticals. N.V.D. is currently an employee of Genentech, and is a stockholder in Roche. A.T.L. is a shareholder in LightHorse Therapeutics and is a consultant/advisory board member for LightHorse Therapeutics and Omega Therapeutics. M.W.Z. is currently an employee and shareholder in Foghorn Therapeutics. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu