Alternative splicing of apoptosis-related genes in imatinib-treated K562 cells identified by exon array analysis.

Abstract:

:Imatinib is the therapeutic standard for newly diagnosed patients with chronic myeloid leukemia (CML). In these patients, imatinib has been shown to induce an apoptotic response specifically in cells expressing the oncogenic fusion protein BCR-ABL. Previous studies in our lab revealed that imatinib-induced apoptosis in K562 cells involves a shift in production of Bcl-x splice isoforms towards the pro-apoptotic Bcl-xs splice variant. Here, we report the findings from our subsequent study to identify other apoptosis-related genes that are differentially spliced in response to imatinib treatment. Gene expression profiling of imatinib-treated K562 cells was performed by the Affymetrix GeneChip Human Exon 1.0 ST array, and differences in exon-level expression and alternative splicing were analyzed using the easyExon software. Detailed analysis by reverse transcription-PCR (RT-PCR) and sequencing of key genes confirmed the experimental results of the exon array. Our results suggest that imatinib treatment of K562 cells causes a transcriptional shift towards alternative splicing in a large number of apoptotic genes. The present study provides insight into the molecular character of apoptotic leukemia cells and may help to improve the mechanism of imatinib therapy in patients with CML.

journal_name

Int J Mol Med

authors

Liu J,Xiao Y,Xiong HM,Li J,Huang B,Zhang HB,Feng DQ,Chen XM,Wang XZ

doi

10.3892/ijmm.2011.872

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

690-8

issue

4

eissn

1107-3756

issn

1791-244X

journal_volume

29

pub_type

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