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.

• MeSH
• anaplastická lymfomová kináza genetika   metabolismus   MeSH
• anaplastický velkobuněčný lymfom * genetika   metabolismus   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• Janus kinasy metabolismus   MeSH
• karcinogeneze genetika   MeSH
• lidé MeSH
• nádorová transformace buněk MeSH
• signální transdukce * genetika   MeSH
• transkripční faktor STAT3 genetika   MeSH
• transkripční faktory STAT metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anaplastická lymfomová kináza MeSH
• Janus kinasy MeSH
• STAT3 protein, human MeSH Prohlížeč
• transkripční faktor STAT3 MeSH
• transkripční faktory STAT MeSH

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

• MeSH
• hematologické nádory * MeSH
• lidé MeSH
• lymfom * patologie   MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH