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Alternative expression of TCRzeta related genes in patients with chronic myeloid leukemia.

Authors: Zha, X  Yan, X  Shen, Q  Zhang, Y  Wu, X  Chen, S  Li, B  Yang, L  Geng, S  Weng, J  Du, X  Li, Y 
Citation: Zha X, etal., J Hematol Oncol. 2012 Dec 10;5:74. doi: 10.1186/1756-8722-5-74.
Pubmed: (View Article at PubMed) PMID:23228155
DOI: Full-text: DOI:10.1186/1756-8722-5-74

A previous study has demonstrated a significant decrease in the TCRzeta gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRzeta-regulating factors, the distribution of the TCRzeta 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcepsilonRIgamma and ZAP-70 genes. TCRzeta 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 TCRzeta, FcepsilonRIgamma, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRzeta gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIgamma 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) TCRzeta 3'-UTR and alternatively splieced (AS) TCRzeta 3'-UTR which have been alternatively splieced in the WT TCRzeta 3'-UTR . However, 35% of the CML cases contained only the wild type TCRzeta 3'-UTR isoform. Based on the TCRzeta 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 TCRzeta 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCRzeta 3'-UTR isoforms. A significantly different ASF/SF-2 and FcepsilonRIgamma gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCRzeta 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 TCRzeta 3'-UTR, is thought to participate in feedback regulation. The characteristics of TCRzeta 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.


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CRRD Object Information
CRRD ID: 11038774
Created: 2016-02-24
Species: All species
Last Modified: 2016-02-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.