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

<p>Abstract</p> <p>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'...

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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
Published: BMC 2012-12-01
Series:Journal of Hematology & Oncology
Subjects:
Online Access:http://www.jhoonline.org/content/5/1/74
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author Zha Xianfeng
Yan Xiaojuan
Shen Qi
Zhang Yuping
Wu Xiuli
Chen Shaohua
Li Bo
Yang Lijian
Geng Suxia
Weng Jianyu
Du Xin
Li Yangqiu
author_facet Zha Xianfeng
Yan Xiaojuan
Shen Qi
Zhang Yuping
Wu Xiuli
Chen Shaohua
Li Bo
Yang Lijian
Geng Suxia
Weng Jianyu
Du Xin
Li Yangqiu
author_sort Zha Xianfeng
collection DOAJ
description <p>Abstract</p> <p>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<sup>+</sup>AS<sup>-</sup> CML group, containing patients that express only the wild type TCRζ 3'-UTR, and the WT<sup>+</sup>AS<sup>+</sup> 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<sup>+</sup>AS<sup>-</sup> and WT<sup>+</sup>AS<sup>+</sup>CML groups. We concluded that defective TCRζ expression may be characterized in the WT<sup>+</sup>AS<sup>-</sup>and WT<sup>+</sup>AS<sup>+</sup>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.</p>
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spelling doaj.art-e2c16afe6d8c43e28f86a3e396a4574f2022-12-22T01:19:34ZengBMCJournal of Hematology & Oncology1756-87222012-12-01517410.1186/1756-8722-5-74Alternative expression of TCRζ related genes in patients with chronic myeloid leukemiaZha XianfengYan XiaojuanShen QiZhang YupingWu XiuliChen ShaohuaLi BoYang LijianGeng SuxiaWeng JianyuDu XinLi Yangqiu<p>Abstract</p> <p>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<sup>+</sup>AS<sup>-</sup> CML group, containing patients that express only the wild type TCRζ 3'-UTR, and the WT<sup>+</sup>AS<sup>+</sup> 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<sup>+</sup>AS<sup>-</sup> and WT<sup>+</sup>AS<sup>+</sup>CML groups. We concluded that defective TCRζ expression may be characterized in the WT<sup>+</sup>AS<sup>-</sup>and WT<sup>+</sup>AS<sup>+</sup>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.</p>http://www.jhoonline.org/content/5/1/74ASF/SF-2geneTCRζ3<sup>′</sup>-UTRTCRζ geneFcεRIγ geneChronic myeloid leukemiaReal-time PCR
spellingShingle Zha Xianfeng
Yan Xiaojuan
Shen Qi
Zhang Yuping
Wu Xiuli
Chen Shaohua
Li Bo
Yang Lijian
Geng Suxia
Weng Jianyu
Du Xin
Li Yangqiu
Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
Journal of Hematology & Oncology
ASF/SF-2gene
TCRζ3<sup>′</sup>-UTR
TCRζ gene
FcεRIγ gene
Chronic myeloid leukemia
Real-time PCR
title Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
title_full Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
title_fullStr Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
title_full_unstemmed Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
title_short Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
title_sort alternative expression of tcrζ related genes in patients with chronic myeloid leukemia
topic ASF/SF-2gene
TCRζ3<sup>′</sup>-UTR
TCRζ gene
FcεRIγ gene
Chronic myeloid leukemia
Real-time PCR
url http://www.jhoonline.org/content/5/1/74
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