Alternative splicing of apoptosis-related genes in imatinib-treated             K562 cells identified by exon array analysis.
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.
Department of Clinical Laboratory, Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
Jing
J
Liu
Yun
Y
Xiao
Huo-Mei
HM
Xiong
Jing
J
Li
Bo
B
Huang
Hai-Bin
HB
Zhang
Dan-Qin
DQ
Feng
Xi-Min
XM
Chen
Xiao-Zhong
XZ
Wang
D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics*; D001549:Benzamides; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D046228:Microarray Analysis / Q000379:methods*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
C494811:BCL2L1 protein, human; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012334:RNA, Neoplasm; D051020:bcl-X Protein; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl