Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.

Published

Journal Article

Human aggressive B-cell non-Hodgkin lymphomas (NHL) encompass the continuum between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL), and display considerable clinical and biologic heterogeneity, most notably related to therapy response. We previously showed that lymphomas arising in the Eμ-Myc transgenic mouse are heterogeneous, mirroring genomic differences between Burkitt lymphoma and DLBCL. Given clinical heterogeneity in NHL and the need to develop strategies to match therapeutics with discrete forms of disease, we investigated the extent to which genomic variation in the Eμ-Myc model predicts response to therapy. We used genomic analyses to classify Eμ-Myc lymphomas, link Eμ-Myc lymphomas with NHL subtypes, and identify lymphomas with predicted resistance to conventional and NF-κB-targeted therapies. Experimental evaluation of these predictions links genomic profiles with distinct outcomes to conventional and targeted therapies in the Eμ-Myc model, and establishes a framework to test novel targeted therapies or combination therapies in specific genomically defined lymphoma subgroups. In turn, this will rationally inform the design of new treatment options for aggressive human NHL.

Full Text

Duke Authors

Cited Authors

  • Rempel, RE; Jiang, X; Fullerton, P; Tan, TZ; Ye, J; Lau, JA; Mori, S; Chi, J-T; Nevins, JR; Friedman, DR

Published Date

  • December 2014

Published In

Volume / Issue

  • 13 / 12

Start / End Page

  • 3219 - 3229

PubMed ID

  • 25349303

Pubmed Central ID

  • 25349303

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

International Standard Serial Number (ISSN)

  • 1535-7163

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-13-0044

Language

  • eng