E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction

Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6250-5. doi: 10.1073/pnas.0901166106. Epub 2009 Mar 30.


Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Emu-TCL1 transgenic mouse model. With development of leukemia, Emu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Emu-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Disease Progression
  • Gene Expression Profiling
  • Humans
  • Immunological Synapses / drug effects
  • Immunological Synapses / immunology
  • Immunological Synapses / pathology
  • Immunotherapy*
  • Lenalidomide
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology*
  • Thalidomide / analogs & derivatives
  • Thalidomide / pharmacology


  • Proto-Oncogene Proteins
  • Tcl1 protein, mouse
  • Thalidomide
  • Lenalidomide

Associated data

  • GEO/GSE8836