STAT3 Dysregulation in Mature T and NK Cell Lymphomas.

Autor: Seffens A; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. ams2494@cumc.columbia.edu.; Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. ams2494@cumc.columbia.edu., Herrera A; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. alberto.herrera@nyumc.org., Tegla C; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. cosmin.tegla@nyumc.org., Buus TB; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. terkild.buus@sund.ku.dk.; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen DK2200, Denmark. terkild.buus@sund.ku.dk., Hymes KB; Division of Hematology/Oncology, New York University School of Medicine, New York, NY 10016, USA. kenneth.hymes@nyulangone.org., Ødum N; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen DK2200, Denmark. ndum@sund.ku.dk., Geskin LJ; Department of Dermatology, Columbia University, New York, NY 10032, USA. ljg2145@cumc.columbia.edu., Koralov SB; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Sergei.Koralov@nyumc.org.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2019 Nov 02; Vol. 11 (11). Date of Electronic Publication: 2019 Nov 02.
DOI: 10.3390/cancers11111711
Abstrakt: A bstract : T cell lymphomas comprise a distinct class of non-Hodgkin's lymphomas, which include mature T and natural killer (NK) cell neoplasms. While each malignancy within this group is characterized by unique clinicopathologic features, dysregulation in the Janus tyrosine family of kinases/Signal transducer and activator of transcription (JAK/STAT) signaling pathway, specifically aberrant STAT3 activation, is a common feature among these lymphomas. The mechanisms driving dysregulation vary among T cell lymphoma subtypes and include activating mutations in upstream kinases or STAT3 itself, formation of oncogenic kinases which drive STAT3 activation, loss of negative regulators of STAT3, and the induction of a pro-tumorigenic inflammatory microenvironment. Constitutive STAT3 activation has been associated with the expression of targets able to increase pro-survival signals and provide malignant fitness. Patients with dysregulated STAT3 signaling tend to have inferior clinical outcomes, which underscores the importance of STAT3 signaling in malignant progression. Targeting of STAT3 has shown promising results in pre-clinical studies in T cell lymphoma lines, ex-vivo primary malignant patient cells, and in mouse models of disease. However, targeting this pleotropic pathway in patients has proven difficult. Here we review the recent contributions to our understanding of the role of STAT3 in T cell lymphomagenesis, mechanisms driving STAT3 activation in T cell lymphomas, and current efforts at targeting STAT3 signaling in T cell malignancies.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje