Overexpression of MALT1-A20-NF-κB in adult B-cell acute lymphoblastic leukemia

Cancer Cell International

Yangqiu Li¹  Xiuli Wu²  Kanger Zhu¹  Gengxin Luo¹  Lijian Yang²  Shaohua Chen²  Ling Xu²  Jing Lai²  Li Xuan³  Xu Wang⁴  Junyan Hu⁵  Yi Xu² 

[1] Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou 510632, China;Institute of Hematology, Jinan University, Guangzhou 510632, China;Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, China;Department of Emergency, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China

关键词: NF-κB;    MALT1;    A20;    B-cell acute lymphoblastic leukemia;   

Others  :  1230692
DOI  :  10.1186/s12935-015-0222-0

 received in 2015-01-22, accepted in 2015-07-02,  发布年份 2015

【 摘 要 】

Background

A20 is a dual inhibitor of NF-κB activation and apoptosis in the tumor necrosis factor receptor 1 signaling pathway, and both are related to tumorigenesis. A20 is frequently inactivated by deletions and/or mutations in several B and T cell lymphoma subtypes; however, knowledge of the role of A20 in B-cell acute lymphoblastic leukemia (B-ALL) remains limited. In this study, we characterized the A20 gene expression pattern, the expression level of its upstream regulating factor MALT1, and its downstream target NF-κB in adult B-ALL.

Methods

The expression level of MALT1, A20 and NF-κB1 was detected in peripheral blood mononuclear cells (PBMCs) from 20 patients with adult B-ALL (including 12 de novo B-ALL and 8 refractory/relapse B-ALL cases), and nine patients with B-ALL in complete remission (CR) using real-time PCR. Sixteen healthy individuals served as controls.

Results

Significant A20 overexpression was found in the B-ALL (median: 13.489) compared with B-ALL CR (median: 3.755) (P = 0.003) patients and healthy individuals (median: 8.748) (P = 0.002), while there was no significant difference in A20 expression between B-ALL CR patients and healthy individuals (P = 0.107). Interestingly, the A20 expression level in the B-ALL samples was relatively different with approximately 50% of the B-ALL cases showing a relatively high A20 expression level, while the remaining 50% cases demonstrated slight upregulation or a similar expression level as the healthy controls. However, there was no significant difference in the A20 expression level between de novo B-ALL (median 12.252) and refractory/relapse B-ALL patients (median 21.342) (P = 0.616). Similarly, a significantly higher expression level of NF-κB1 was found in the B-ALL (median 1.062) patients compared with healthy individuals (median 0.335) (P < 0.0001), while the NF-κB1 expression level was downregulated in the B-ALL CR group (median 0.339), which was significantly lower than that in those with B-ALL (P = 0.001). Moreover, the MALT1 expression level in B-ALL was upregulated (median 1.938) and significantly higher than that in healthy individuals (median 0.677) (P = 0.002) and B-ALL CR patients (median 0.153) (P = 0.008). The correlation of the expression levels of all three genes was lost in B-ALL.

Conclusions

We found that MALT1-A20-NF-κB is overexpressed in adult B-ALL, which may be related to the pathogenesis of B-ALL, and this pathway may be considered a potentially attractive target for the development of B-ALL therapeutics.

【 授权许可】

   
2015 Xu et al.

【 图 表 】

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