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AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies
By misdirecting the activity of Activation-Induced Deaminase (AID) to a conditional MYC transgene, we have achieved sporadic, AID-dependent MYC activation in germinal center B cells of Vk ∗MYC mice. Whereas control C57BL/6 mice develop benign monoclonal gammopathy with age, all Vk ∗MYC mice progress...
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Published in: | Cancer cell 2008-02, Vol.13 (2), p.167-180 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | By misdirecting the activity of Activation-Induced Deaminase (AID) to a conditional
MYC transgene, we have achieved sporadic, AID-dependent
MYC activation in germinal center B cells of Vk
∗MYC mice. Whereas control C57BL/6 mice develop benign monoclonal gammopathy with age, all Vk
∗MYC mice progress to an indolent multiple myeloma associated with the biological and clinical features highly characteristic of the human disease. Furthermore, antigen-dependent myeloma could be induced by immunization with a T-dependent antigen. Consistent with these findings in mice, more frequent
MYC rearrangements, elevated levels of MYC mRNA, and
MYC target genes distinguish human patients with multiple myeloma from individuals with monoclonal gammopathy, implicating a causal role for
MYC in the progression of monoclonal gammopathy to multiple myeloma. |
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ISSN: | 1535-6108 1878-3686 |
DOI: | 10.1016/j.ccr.2008.01.007 |