@article{7023aa1f511749adb5d518aaf14122d5,
title = "AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies",
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.",
keywords = "CELLBIO",
author = "Marta Chesi and Robbiani, {Davide F.} and Michael Sebag and Chng, {Wee Joo} and Maurizio Affer and Rodger Tiedemann and Riccardo Valdez and Palmer, {Stephen E.} and Haas, {Stephanie S.} and Stewart, {A. Keith} and Rafael Fonseca and Richard Kremer and Giorgio Cattoretti and Bergsagel, {P. Leif}",
note = "Funding Information: This work was supported by grants from the National Institute of Health RO1-AG020686 (P.L.B.), RO1-CA83724 (R.F.), RO1-CA129009 (A.K.S.), SPORE P50-CA100707 (R.F. and P.L.B.), P01-CA62242 (R.F.) and funding from the Multiple Myeloma Research Foundation (M.A. and M.S.) and the Fund to Cure Myeloma (P.L.B.). R.F. is a Clinical Investigator of the Damon Runyon Cancer Research Fund. We thank Dr. M. Nussenzweig for discussion and for donating the AID null mice and K. Colon for assistance with mouse bleeding and genotyping. We thank Dr. Herbert Morse for histologic review and Dr. Paul Szabo for assistance with eastern blots. We are grateful to Dr. Freda Stevenson for critical review of the manuscript and to Dr. Mike Kuehl for suggesting a role for MYC in the MGUS-to-MM progression in human. ",
year = "2008",
month = feb,
day = "5",
doi = "10.1016/j.ccr.2008.01.007",
language = "English (US)",
volume = "13",
pages = "167--180",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}