title: Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.
abstract: 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.
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Rempel
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Paul
authors.initials: P
authors.lastname: Fullerton
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Jieru
authors.initials: J
authors.lastname: Ye
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Jieying Amelia
authors.initials: JA
authors.lastname: Lau
authors.affiliation: The Cancer Institute, Japanese Foundation of Cancer Research, Tokyo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mori
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Jen-Tsan
authors.initials: JT
authors.lastname: Chi
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina. Department of Medicine, Duke University Medical Center, Durham, North Carolina. Durham Veterans Affairs Medical Center, Durham, North Carolina. daphne.friedman@duke.edu.
authors.forename: Daphne R
authors.initials: DR
authors.lastname: Friedman
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016000:Cluster Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D016896:Treatment Outcome