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Status |
Public on Dec 01, 2007 |
Title |
CLL in Em-TCL1 mice provides a biologically relevant model to unravel and reverse immune deficiency in human cancer. |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Keywords: comparative gene expression profiling analysis.
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Overall design |
CD4 T cells and CD8 T cells were obtained from spleens of B6C3 and Em-TCL1 transgenic murine model of CLL or from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals (Pubmed ID: 15965501). Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of CLL to healthy within or between the species.
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Contributor(s) |
Görgün G, Holderried TA, Ramsay AG, Zahrieh D, Liu F, Quackenbush J, Croce CM, Gribben JG |
Citation(s) |
19332800 |
Submission date |
Aug 21, 2007 |
Last update date |
Feb 11, 2019 |
Contact name |
Gullu Gorgun |
E-mail(s) |
gullu_gorgun@dfci.harvard.edu
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Phone |
617 632 3358
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Fax |
617 632 3222
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Organization name |
Dana-Farber Cancer Institute
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Department |
Medical Oncology
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Street address |
44 Binney Street
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02115 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (56)
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Relations |
BioProject |
PRJNA102173 |