Dataset Information

BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma.

ABSTRACT: The current treatment for natural killer/T-cell lymphoma (NKTL) among advanced/relapsed patients is unsatisfying, thereby highlighting the need for novel therapeutic targets. B-cell chronic lymphocytic leukemia/lymphoma 11 A (BCL11A), as a transcription factor, is oncogenic in several neoplasms. However, its function in NKTL remains unclear. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure the BCL11A expression levels among NKTL patients and in NKTL cell lines. Natural killer (NK) cells from healthy subjects were used as negative control. Transient transfection with small interfering RNA was used to knockdown the expression in NKTL cell lines. Samples and clinical histories were collected from 343 NKTL patients (divided into test and validation groups) to evaluate the clinical value of BCL11A expression level. The BCL11A expression was upregu\lated among NKTL patients and in NKTL cell lines. Reduced cell proliferation and increased apoptosis were observed after silencing BCL11A in NKTL cell lines. BCL11A expression level was correlated with RUNX3, c-MYC, and P53 in NKTL. Notably, a high BCL11A expression was correlated with unfavorable clinical characteristics and predicted poor outcomes in NKTL. In conclusion, BCL11A was overexpressed in NKTL, while its upregulation promoted tumor development. Therefore, BCL11A expression level may be a promising prognostic biomarker for NKTL.

SUBMITTER: Shi H

PROVIDER: S-EPMC7311857 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma.

Shi Hongyun H Li Chun C Feng Wei W Yue Jianjun J Song Jingfang J Peng Aizhi A Wang Hua H

Frontiers in pharmacology 20200604

The current treatment for natural killer/T-cell lymphoma (NKTL) among advanced/relapsed patients is unsatisfying, thereby highlighting the need for novel therapeutic targets. B-cell chronic lymphocytic leukemia/lymphoma 11 A (BCL11A), as a transcription factor, is oncogenic in several neoplasms. However, its function in NKTL remains unclear. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure the BCL11A expression levels among NKTL patients and in NKTL ...[more]

PMID: 32625084

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Project description:Extranodal natural killer/T-cell lymphoma, nasal type (ENKL), is a rare malignancy of Non-Hodgkin lymphoma characterized by an aggressive clinical course and poor prognosis. It shows strong association with Epstein-Barr virus infection and occurs more commonly in Asia and Latin America. Various genetic alterations have been identified in ENKL by gene expression profiling and sequencing techniques. The frequent deletion of chromosome 6q21 was reported to lead to the silence of several tumor suppressor genes. Also, there have been novel genetic mutations that were recently uncovered and were found to frequently activate several oncogenic pathways, including the JAK/STAT, NF-?B, and MAPK pathways. Besides, we believe that deregulated single genes and epigenetic dysregulation might be relevant to the mechanism of this disease and thus, may have the potential to shed lights on the development of new therapeutic strategies. The consensus on the standard treatment for ENKL has not yet been currently established. For localized ENKL patients, radiotherapy with concurrent chemotherapy and sequential patterns of chemotherapy and radiotherapy are recommended as first-line therapy. As for advanced or relapsed/refractory ENKL patients, the application of non-anthracycline-containing regimens have significantly improved the clinical outcome, contributing to higher response rate, longer overall survival and progression-free survival. Hematopoietic stem cell transplantation is widely recommended for consolidation after a complete remission or partial remission has been achieved. The anti-programmed death 1 antibody, an immune checkpoint inhibitor, has demonstrated favorable results in treating relapsed or refractory ENKL. Of the current ENKL treatment, researchers are still striving to validate how radiotherapy and chemotherapy should be optimally combined and which of the non-anthracycline-containing regimens is superior. In this review, we summarize the main genetic alterations frequently found in ENKL and their role in providing new insights into the therapeutic targets of this disease, and highlight the recent findings regarding new biologic markers, novel therapeutic strategies applied to this intriguing neoplasm.

Dataset Information

BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma.

Publications

BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma.

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