The 3' IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2007

The 3' IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype.

Résumé

Burkitt lymphoma (BL) features translocations linking c-myc to an Ig locus. Breakpoints in the H chain locus (IgH) stand either close to J(H) or within switch regions and always link c-myc to the 3' IgH locus control region (3' LCR). To test the hypothesis that the 3' LCR alone was sufficient to deregulate c-myc, we generated mice carrying a 3' LCR-driven c-myc transgene and specifically up-regulating c-myc in B cells. Splenic B cells from mice proliferated exaggeratedly in response to various signals had an elevated apoptosis rate but normal B220/IgM/IgD expression. Although all Ig levels were lowered in vivo, class switching and Ig secretion proved normal in vitro. Beginning at the age of 12 wk, transgenic mice developed clonal lymphoblastic lymphomas or diffuse anaplastic plasmacytomas with an overall incidence of 80% by 40 wk. Lymphoblastic lymphomas were B220(+)IgM(+)IgD(+) with the BL "starry sky" appearance. Gene expression profiles revealed broad alterations in the proliferation program and the Ras-p21 pathway. Our study demonstrates that 3' IgH enhancers alone can deregulate c-myc and initiate the development of BL-like lymphomas. The rapid and constant occurrence of lymphoma in this model makes it valuable for the understanding and the potential therapeutic manipulation of c-myc oncogenicity in vivo.

Domaines

Immunologie
Fichier non déposé

Dates et versions

hal-00181178 , version 1 (23-10-2007)

Identifiants

  • HAL Id : hal-00181178 , version 1
  • PUBMED : 17947677

Citer

Véronique Truffinet, Eric Pinaud, Nadine Cogné, Barbara Petit, Laurence Guglielmi, et al.. The 3' IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype.. Journal of Immunology, 2007, 179 (9), pp.6033-6042. ⟨hal-00181178⟩
77 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More