Imatinib mesylate directly impairs class switch recombination through down-regulation of AID: its potential efficacy as an AID suppressor
| Autor: | Hitoshi Nagaoka, Kiyoshi Ando, Ai Kotani, Takae Toyoshima, Jun Lu, Tadayuki Sato, Kazuaki Yokoyama, Yasutoshi Agata, Naoya Nakamura, Masafumi Tanaka, Toyotaka Kawamata, Arinobu Tojo, Naoki Oyaizu |
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| Rok vydání: | 2012 |
| Předmět: |
Immunology
Drug Evaluation Preclinical Down-Regulation Somatic hypermutation medicine.disease_cause Biochemistry Piperazines law.invention Hypogammaglobulinemia Mice law Cytidine Deaminase hemic and lymphatic diseases Animals Medicine Recombination Genetic Sheep business.industry Myeloid leukemia Cell Biology Hematology Cytidine deaminase medicine.disease Immunoglobulin Class Switching Mice Inbred C57BL Pyrimidines Treatment Outcome Imatinib mesylate Immunoglobulin class switching Benzamides Imatinib Mesylate Cancer research Suppressor Somatic Hypermutation Immunoglobulin business Carcinogenesis Immunosuppressive Agents |
| Zdroj: | Blood. 119:3123-3127 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2011-01-327932 |
| Popis: | Activation-induced cytidine deaminase (AID) is essential for class switch recombination and somatic hypermutation. 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 often develop hypogammaglobulinemia, the mechanism of which has not yet been clarified. Here, we provide evidence that class switch recombination on B-cell activation is apparently inhibited by IM through down-regulation 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. |
| Databáze: | OpenAIRE |
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