Author/Authors :
Chesi، نويسنده , , Marta and Robbiani، نويسنده , , Davide F. and Sebag، نويسنده , , Michael T. Chng، نويسنده , , Wee Joo and Affer، نويسنده , , Maurizio and Tiedemann، نويسنده , , Rodger and Valdez، نويسنده , , Riccardo and Palmer، نويسنده , , Stephen E. and Haas، نويسنده , , Stephanie S. and Stewart، نويسنده , , A. Keith and Fonseca، نويسنده , , Rafael and Kremer، نويسنده , , Richard and Cattoretti، نويسنده , , Giorgio and Bergsagel، نويسنده , , P. Leif، نويسنده ,
Abstract :
Summary
directing 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.
