Imatinib mesylate directly impairs class switch recombination through down-regulation of AID: its potential efficacy as an AID suppressor-Reference-Cited by-同舟云学术

Imatinib mesylate directly impairs class switch recombination through down-regulation of AID: its potential efficacy as an AID suppressor

Published:2012-03-29 Issue:13 Volume:119 Page:3123-3127
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Kawamata Toyotaka¹,Lu Jun²,Sato Tadayuki³,Tanaka Masafumi⁴,Nagaoka Hitoshi⁵,Agata Yasutoshi⁶,Toyoshima Takae²,Yokoyama Kazuaki¹,Oyaizu Naoki⁷,Nakamura Naoya⁸,Ando Kiyoshi⁹,Tojo Arinobu¹,Kotani Ai²

Affiliation:

1. Department of Hematology-Oncology/Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan;

2. Institute of Innovation Science and Technology, Tokai University, Kanagawa, Japan;

3. Center for Education and Support, Department of Medicine, Tokai University, Kanagawa, Japan;

4. Molecular Life Science, Department of Medicine, Tokai University, Kanagawa, Japan;

5. Molecular Pathology, Department of Medicine, Gifu University, Gifu, Japan;

6. Immunology, Department of Medicine, Kyoto University, Kyoto, Japan;

7. Department of Laboratory Medicine in Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan;

8. Pathology, School of Medicine, Tokai University, Kanagawa, Japan; and

9. Hematology and Oncology, School of Medicine, Tokai University, Kanagawa, Japan

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/119/13/3123/1349549/zh801312003123.pdf

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