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

Xianfeng Zha1, Xiaojuan Yan1, Qi Shen1, Yuping Zhang2, Xiuli Wu1, Shaohua Chen1, Bo Li1, Lijian Yang1, Suxia Geng3, Jianyu Weng3, Xin Du3 and Yangqiu Li14*

Author Affiliations

1 Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China

2 Department of Hematology, Guangzhou First Municipal People’s Hospital Affiliated to Guangzhou Medical College, Guangzhou, 510180, People’s Republic of China

3 Department of Hematology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou, 510080, China

4 Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China

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Journal of Hematology & Oncology 2012, 5:74  doi:10.1186/1756-8722-5-74

Published: 10 December 2012

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.

Keywords:
ASF/SF-2gene; TCRζ3-UTR; TCRζ gene; FcεRIγ gene; Chronic myeloid leukemia; Real-time PCR