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Cancer Cell. 2008 Feb;13(2):167-80. doi: 10.1016/j.ccr.2008.01.007.

AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies.

Author information

1
Comprehensive Cancer Center, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. chesi.marta@mayo.edu <chesi.marta@mayo.edu>

Abstract

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.

PMID:
18242516
PMCID:
PMC2255064
DOI:
10.1016/j.ccr.2008.01.007
[Indexed for MEDLINE]
Free PMC Article

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