STAT3 Dysregulation in Mature T and NK Cell Lymphomas

被引:29
作者
Seffens, Angelina [1 ,2 ]
Herrera, Alberto [1 ]
Tegla, Cosmin [1 ]
Buus, Terkild B. [1 ,3 ]
Hymes, Kenneth B. [4 ]
Odum, Niels [3 ]
Geskin, Larisa J. [5 ]
Koralov, Sergei B. [1 ]
机构
[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[2] Columbia Univ, Vagelos Coll Phys & Surg, New York, NY 10032 USA
[3] Univ Copenhagen, LEO Fdn, Dept Immunol & Microbiol, Skin Immunol Res Ctr, DK-2200 Copenhagen, Denmark
[4] NYU, Div Hematol Oncol, Sch Med, New York, NY 10016 USA
[5] Columbia Univ, Dept Dermatol, New York, NY 10032 USA
关键词
STAT3; T cell lymphoma; lymphomagenesis; JAK; STAT; ANAPLASTIC LYMPHOMA; MYCOSIS-FUNGOIDES; TYROSINE PHOSPHORYLATION; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTOR; THERAPEUTIC TARGET; SIGNAL TRANSDUCER; SEZARY-SYNDROME; DOWN-REGULATION; INHIBITS STAT3;
D O I
10.3390/cancers11111711
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:17
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