Alternative expression of TCR? related genes in patients with chronic myeloid leukemia.
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ABSTRACT: A previous study has demonstrated a significant decrease in the TCR? gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCR?-regulating factors, the distribution of the TCR? 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), Fc?RI? and ZAP-70 genes. TCR? 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 TCR?, Fc?RI?, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCR? gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRI? 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) TCR? 3'-UTR and alternatively splieced (AS) TCR? 3'-UTR which have been alternatively splieced in the WT TCR? 3'-UTR . However, 35% of the CML cases contained only the wild type TCR? 3'-UTR isoform. Based on the TCR? 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 TCR? 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCR? 3'-UTR isoforms. A significantly different ASF/SF-2 and Fc?RI? gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCR? 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 TCR? 3'-UTR, is thought to participate in feedback regulation. The characteristics of TCR? 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.
SUBMITTER: Zha X
PROVIDER: S-EPMC3544630 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
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