AID-dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-germinal Center Malignancies

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2008 Feb 5

PMID 18242516

Citations 229

Authors

Marta Chesi

Davide F Robbiani

Michael Sebag

Wee Joo Chng

Maurizio Affer

Rodger Tiedemann

Riccardo Valdez

Stephen E Palmer

Stephanie S Haas

A Keith Stewart

Rafael Fonseca

Richard Kremer

Giorgio Cattoretti

P Leif Bergsagel

Affiliations

Soon will be listed here.

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.

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