| AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. | |
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MedLine Citation:
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PMID: 20357822 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID) diversifies immunoglobulin through somatic hypermutation (SHM) and class-switch recombination (CSR). AID-transgenic mice develop T-lymphoma, indicating that constitutive expression of AID leads to tumorigenesis. Here, we transplanted mouse bone marrow cells transduced with AID. Twenty-four of the 32 recipient mice developed T-lymphoma 2-4 months after the transplantation. Surprisingly, unlike AID-transgenic mice, seven recipients developed B-leukemia/lymphoma with longer latencies. None of the mice suffered from myeloid leukemia. When we used nude mice as recipients, they developed only B-leukemia/lymphoma, presumably due to lack of thymus. Analysis of AID mutants suggested that an intact form with SHM activity is required for maximum ability of AID to induce lymphoma. Except for a K-ras active mutant in one case, specific mutations could not be identified in T-lymphoma; however, Notch1 was constitutively activated in most cases. Importantly, truncations of Ebf1 or Pax5 were observed in B-leukemia/lymphoma. In conclusion, this is the first report on the potential of AID overexpression to promote B-cell lymphomagenesis in a mouse model. Aberrant expression of AID in bone marrow cells induced leukemia/lymphoma in a cell-lineage-dependent manner, mainly through its function as a mutator. |
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Authors:
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Y Komeno; J Kitaura; N Watanabe-Okochi; N Kato; T Oki; F Nakahara; Y Harada; H Harada; R Shinkura; H Nagaoka; Y Hayashi; T Honjo; T Kitamura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-01 |
Journal Detail:
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Title: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K Volume: 24 ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-06-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 1018-24 Citation Subset: IM |
Affiliation:
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Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Southern Blotting, Western Bone Marrow Transplantation* Cytidine Deaminase / physiology* Disease Models, Animal* Flow Cytometry Lymphoma, T-Cell / etiology*, pathology Mice Mice, Inbred C57BL Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / etiology*, pathology RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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