Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma.
نویسندگان
چکیده
STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration. Whole-transcriptome profiling revealed that STAT3 acts as both a transcriptional activator and a suppressor, with a comparable number of up- and down-regulated genes. STAT3 regulates multiple oncogenic signaling pathways, including NF-κB, a cell-cycle checkpoint, PI3K/AKT/mTORC1, and STAT3 itself. In addition, STAT3 negatively regulates the lethal type I IFN signaling pathway by inhibiting expression of IRF7, IRF9, STAT1, and STAT2 Inhibition of STAT3 activity by ruxolitinib synergizes with the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL cells in vitro and in a xenograft mouse model. Therefore, this study provides a mechanistic rationale for clinical trials to evaluate ruxolitinib or a specific JAK1 inhibitor combined with lenalidomide in ABC DLBCL.
منابع مشابه
miR-4284 and miR-4484 as Putative Biomarkers for Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013.The aim of thi...
متن کاملHISTIOCYTE-RICH B-CELL LYMPHOMA: A CASE REPORT OF A RARE VARIANT OF DIFFUSE LARGE B-CELL LYMPHOMA
The authors describe a case of histiocyte-rich B-cell lymphoma (HR-BCL), a variant of diffuse large B-cell lymphoma, in a 51-year-old man. The patient presented with large axillary lymphadenopathy. Histopathologic and immunohistochemical examination of lymph node biopsy revealed diffuse effacement of the lymph node architecture by reactive histiocytes and neoplastic CD20 positive B cells. ...
متن کاملA systematic review evaluating the efficacy of autologous hematopoietic transplantation for diffuse large B cell lymphoma-type Richter syndrome
Background: Chronic lymphocytic leukemia (CLL) can transform into fast growing lymphoma for diffuse large B-cell lymphoma (DLBCL) called Richter's syndrome (RS), which is commonly related to an existence of large B-cells with equal or larger size than macrophage nuclei or more than twice those of normal lymphocyte. We conducted a systematic review of the existing literature to assess the clinic...
متن کاملEarly detection of intravascular large B-cell lymphoma by 18FDG-PET/CT with diffuse FDG uptake in the lung without respiratory symptoms or chest CT abnormalities
Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of systemic extranodal non-Hodgkin diffuse large B-cell lymphoma (DLBCL). We report a rare case of IVLBCL who showed diffuse 18F-fluorodeoxyglucose (FDG) uptake in the lung in FDG-positron emission tomography/computed tomography (PET/CT) without respiratory symptoms or chest CT abnormalities. Serum biochemical studies...
متن کاملPrimary Hepatic Diffuse Large B-Cell Lymphoma in a Patient with Scleroderma
Primary Hepatic Lymphoma (PHL) is rare and possibly associated with viral hepatitis and autoimmune diseases. Scleroderma could exceptionally be complicated by lymphoma. We describe PHL occurring in a 52-year-old female suffering scleroderma for eight years, with no history of cytotoxic or high-dose glucocorticoid therapy. CT scan, performed to work-up abdominal discomfort, constipation, and ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 115 3 شماره
صفحات -
تاریخ انتشار 2018