Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia

• Published in: Journal of hematology and oncology 2012-12, Vol.5 (1), p.74-74, Article 74
• Main Authors: Zha, Xianfeng, Yan, Xiaojuan, Shen, Qi, Zhang, Yuping, Wu, Xiuli, Chen, Shaohua, Li, Bo, Yang, Lijian, Geng, Suxia, Weng, Jianyu, Du, Xin, Li, Yangqiu
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adolescent; Adult; Aged; Alternative Splicing; ASF/SF-2gene; Case-Control Studies; Chronic myeloid leukemia; FcεRIγ gene; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Nuclear Proteins - genetics; Protein Isoforms; Rapid Communication; Real-time PCR; Real-Time Polymerase Chain Reaction; Receptors, Antigen, T-Cell - genetics; Receptors, IgE - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA-Binding Proteins - genetics; Serine-Arginine Splicing Factors; TCRζ gene; TCRζ3′-UTR; Young Adult; ZAP-70 Protein-Tyrosine Kinase - genetics
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/1756-8722-5-74

A previous study has demonstrated a significant decrease in the TCRζ gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRζ-regulating factors, the distribution of the TCRζ 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcεRIγ and ZAP-70 genes. TCRζ 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCRζ, FcεRIγ, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRζ gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIγ and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCRζ 3'-UTR and alternatively splieced (AS) TCRζ 3'-UTR which have been alternatively splieced in the WT TCRζ 3'-UTR . However, 35% of the CML cases contained only the wild type TCRζ 3'-UTR isoform. Based on the TCRζ 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT+AS- CML group, containing patients that express only the wild type TCRζ 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCRζ 3'-UTR isoforms. A significantly different ASF/SF-2 and FcεRIγ gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCRζ expression may be characterized in the WT+AS-and WT+AS+CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCRζ 3'-UTR, is thought to participate in feedback regulation. The characteristics of TCRζ 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.