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

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-kappaB) 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-kappaB 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-kappaB 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-kappaB 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-kappaB, and A20 and NF-kappaB was found.

Conclusions:
An abnormal MALT1-A20-NF-kappaB 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.

Author: Xu WangYan XuLichan LiangYi XuChunyan WangLiang WangShaohua ChenLijian YangXiuli WuBo LiGengxin LuoHuo TanWenyu LiYangqiu Li
Credits/Source: Cancer Cell International 2014, 14:36

Published on: 2014-04-26

News Provider: 7thSpace Interactive

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