Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma
نویسندگان
چکیده
Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL.
منابع مشابه
The Evaluation of Immunophenotypes in Diffuse Large B Cell Lymphoma: A Single Center Study
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B lymphocytes. It is known as a heterogeneous disease with variable therapeutic responses and alternative therapies. Morphological and immunophenotypical evaluation of the biopsy specimens can help diagnose DLBCL. Methods: In the current study, 44 patients were chosen from Shaheed Sadoghi Hospital (2010&nda...
متن کاملBCL2 Family Related Genes Expression and Chemotherapy Response in Diffuse Large B-Cell Lymphoma
Background and Objective: Approximately half of patients with diffuse large B-cell lymphoma are cured with current chemotherapy regimens. The purpose of this study was to evaluate Bax and Bcl2 expression and their relationship with the response to chemotherapy. Materials and Methods This study was a prospective analysis on 44 patients with diffuse large B-cell lymphoma. Their specimens we...
متن کاملmiR-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 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 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 کامل