Overexpressed A20 in Refractory/Relapse B-ALL May Serve As a Potential Therapeutic Target
Authors: Xu Yi , Wu Xiuli , Zhang Fan , Liu Sichu , Chen Shaohua , Yang Lijian , Li Bo , Li Yangqiu 
Published: October 2019

Abstract
Abstract 4816
Treatment failure of precursor B-lymphoblastic leukemia (B-ALL), also known as B-cell acute lymphoblastic leukemia and B-cell acute lymphocytic leukemia, remains a formidable problem. The molecular abnormalities responsible for relapse or drug resistance are still not clear. NF-κB-dependent gene expression and apoptosis plays crucial roles in numerous cellular processes, and defects in their regulation may contribute to a variety of diseases like cancers. As a key regulatory component of the cytoplasmic signaling cascade that mediates NF-κB activation in response to DNA damage, the zinc finger-containing protein A20 (also known as TNF-α-induced protein 3, TNFAIP3) has been found to correlate with drug resistance of breast cancer, prostate cancer and acute myeloid leukemia. To investigate the function of A20 in the development of B-ALL, we analyzed the expression levels of A20 and NF-κB genes in peripheral blood mononuclear cells (PBMCs) from patients (aged 3–72 years, median 30.5) with newly diagnosed B-ALL, B-ALL in complete remission (CR), and refractory/relapse B-ALL. Twenty-nine healthy individuals (aged 20–57, median 28) served as controls. We found that the expression levels of A20 in newly diagnosed B-ALL patients (23.450±16.164) and refractory/relapse B-ALL patients (26.108±12.301) were significantly higher than those from healthy controls (9.865±5.370) (P<0.0001, P<0.0001), while the expression levels of A20 in B-ALL CR patients (2.826±2.415) were significantly decreased and was lower than those from healthy controls (P=0.008). The expression levels of NF-κB in newly diagnosed B-ALL patients (2.025±0.986) were significantly higher than healthy controls (0.337±0.311) (P<0.0001), while the expression levels of NF-κB in refractory/relapse B-ALL patients (0.668±0.707) and B-ALL CR patients (0.405±0.172) were similar to healthy group (P=0.057, P=0.559). The expression levels of A20 had a positive correlation with the expression levels of NF-κB in de novo B-ALL (rs=0.7473, P=0.021), however, the expression levels of A20 in refractory/relapse B-ALL and B-ALL CR group did not show significantly correlation with the expression levels of NF-κB. In conclusion, overexpression of A20 is a feature in de novo and refractory/relapse B-ALL, which may loss their negative regulating function for NF-κB. The expression level of A20 may correlate with the clinical stages of B-ALL, indicating A20 might be considered as a prognostic marker of B-ALL and a potential therapeutic target for refractory/relapse B-ALL.

Disclosures:
Xu: National Natural Science Foundation of China (No. 91129720): Research Funding. Wu:National Natural Science Foundation of China (No. 91129720): Research Funding. Zhang:National Natural Science Foundation of China (No. 91129720): Research Funding. Liu:National Natural Science Foundation of China (No. 91129720): Research Funding. Chen:National Natural Science Foundation of China (No. 91129720): Research Funding. Yang:National Natural Science Foundation of China (No. 91129720): Research Funding. Li:National Natural Science Foundation of China (No. 91129720): Research Funding. Li:National Natural Science Foundation of China (No. 91129720): Research Funding.