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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 08, 2012 |
| Title |
Gene expression profile induced by Imatinib |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Activation-induced cytidine deaminase (AID) is essential for class switch recombination (CSR) and somatic hypermutation (SHM). Its deregulated expression acts as a genomic mutator that can contribute to the development of various malignancies. During treatment with imatinib mesylate (IM), patients with chronic myeloid leukemia (CML) often develop hypogammaglobulinemia, the mechanism of which has not yet been clarified. Here, we provide evidence that CSR upon B cell activation is apparently inhibited by IM through downregulation of AID. Furthermore, expression of E2A, a key transcription factor for AID induction, was markedly suppressed by IM. These results elucidate not only the underlying mechanism of IM-induced hypogammaglobulinemia but also its potential efficacy as an AID suppressor.
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| Overall design |
We investigated that class switch recombination(CSR) upon B cell activation is apparently inhibited by imatinib mesylate(IM) through downregulation of activation-induced cytidine deaminase(AID). Furthermore, expression of E2A was markedly suppressed by IM. To elucidate the more detailed pathway, we performed the microarray analysis.
Microarray analysis was performed on splenocytes cultured for 72 h in the presence or absence of 10 µM Imatinib.
The mouse splenocytes were cultured for 72 h with or without 10 µM Imatinib (IM) in conditioning medium containing IL-4 and LPS. RNA from 1X10^6 splenocytes used for microarray analysis was isolated using the RNeasy Mini Kit (50) (Qiagen, Hilden, Germany). Gene expression microarray analysis was performed using one-color microarray-based gene-expression analysis (Agilent Technologies, Santa Clara, CA, USA) according to the manufacturer’s instructions. After scanning, expression values for the genes were determined using GeneSpringGX software.
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| Contributor(s) |
Kawamata T, Jun L, Sato T, Tanaka M, Nagaoka H, Agata Y, Toyoshima T, Yokoyama K, Oyaizu N, Nakamura N, Ando K, Tojo A, Kotani A |
| Citation(s) |
22337716 |
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| Submission date |
Feb 06, 2012 |
| Last update date |
Nov 01, 2017 |
| Contact name |
toyotaka kawamata |
| E-mail(s) |
[email protected]
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| Organization name |
The Institute of Medical Science,The University of Tokyo
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| Department |
Hematology-Oncology/Molecular therapy
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| Street address |
4-6-1,Shirokanedai,Minato-ku
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| City |
Tokyo |
| ZIP/Postal code |
108-8639 |
| Country |
Japan |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (4)
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| GSM870527 |
in vitro spleen cells 72hr IM(+)_rep1 |
| GSM870528 |
in vitro spleen cells 72hr IM(+)_rep2 |
| GSM870529 |
in vitro spleen cells 72hr IM(-)_rep1 |
| GSM870530 |
in vitro spleen cells 72hr IM(-)_rep2 |
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| Relations |
| BioProject |
PRJNA152679 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35559_RAW.tar |
30.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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