title: Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia.
abstract: 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.
authors.affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zha
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Yan
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C543372:FcepsilonRI gamma-chain, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D017455:Receptors, IgE; C054979:antigen T cell receptor, zeta chain; D000068103:Serine-Arginine Splicing Factors; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human