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Open Access Highly Accessed Primary research

Abnormal expression of A20 and its regulated genes in peripheral blood from patients with lymphomas

Xu Wang12, Yan Xu12, Lichan Liang1, Yi Xu2, Chunyan Wang3, Liang Wang4, Shaohua Chen2, Lijian Yang2, Xiuli Wu12, Bo Li12, Gengxin Luo2, Huo Tan3, Wenyu Li5* and Yangqiu Li12*

Author Affiliations

1 Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, China

2 Institute of Hematology, Jinan University, Guangzhou 510632, China

3 Centre of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510230, China

4 Department of Oncology, First Affiliated Hospital, Jinan University, Guangzhou 510632, China

5 Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China

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Cancer Cell International 2014, 14:36  doi:10.1186/1475-2867-14-36

Published: 26 April 2014

Abstract

Background

Cell-mediated immunity is often suppressed in patients with hematological malignancies. Recently, we found that low T cell receptor (TCR)-CD3 signaling was related to abnormal expression of the negative regulator of nuclear factor kappa B (NF-κB) A20 in acute myeloid leukemia. To investigate the characteristics of T cell immunodeficiency in lymphomas, we analyzed the expression features of A20 and its upstream regulating factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) and genes downstream of NF-κB in patients with different lymphoma subtypes, including T cell non-Hodgkin lymphoma (T-NHL), B cell non-Hodgkin lymphoma (B-NHL) and NK/T cell lymphoma (NK/T-CL).

Methods

Real-time PCR was used to determine the expression level of the MALT1, MALT-V1 (variant 1), A20 and NF-κB genes in peripheral blood mononuclear cells (PBMCs) from 24 cases with T-NHL, 19 cases with B-NHL and 16 cases with NK/T-CL, and 31 healthy individuals (HI) served as control.

Results

Significantly lower A20 and NF-κB expression was found in patients with all three lymphoma subtypes compared with the healthy controls. Moreover, the MALT1 expression level was downregulated in all three lymphoma subtypes. A significant positive correlation between the expression level of MALT1 and A20, MALT1-V1 and A20, MALT1-V1 and NF-κB, and A20 and NF-κB was found.

Conclusions

An abnormal MALT1-A20-NF-κB expression pattern was found in patients with lymphoma, which may result a lack of A20 and dysfunctional MALT1 and may be related to lower T cell activation, which is a common feature in Chinese patients with lymphoma. This finding may at least partially explain the molecular mechanism of T cell immunodeficiency in lymphomas.

Keywords:
Lymphoma; Gene expression; MALT1; A20; NF-κB; T cell immunodeficiency