Epigenetic alterations in a murine model for chronic lymphocytic leukemia

Shih Shih Chen, Mara Sherman, Erin Hertlein, Amy J. Johnson, Michael A. Teitell, John C. Byrd, Christoph Plass

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Early stages in the development of chronic lymphocytic leukemia (CLL) have not been explored mainly due to the inability to study normal B-cells en route to transformation. In order to determine such early events of leukemogenesis, we have used a well established mouse model for CLL. Overexpression of human TCL1, a known CLL oncogene in murine B-cells leads to the development of mature CD19+/CD5+/IgM+ clonal leukemia with a disease phenotype similar to that seen in human CLL. Herein, we review our recent study using this TCL1-driven mouse model for CLL and corresponding human CLL samples in a cross-species epigenomics approach to address the timing and relevance of epigenetic events occurring during leukemogenesis. We demonstrated that the mouse model recapitulates the epigenetic events that have been reported for human CLL, affirming the power and validity of this mouse model to study early epigenetic events in cancer progression. Epigenetic alterations are detected as early as three months after birth, far before disease manifests at about 11 months of age. These mice undergo NFκB repressor complex mediated inactivation of the transcription factor Foxd3, whose targets become aberrantly methylated and silenced in mouse and human CLL. Overall, our data suggest the accumulated epigenetic alterations during CLL pathogenesis as a consequence of gene silencing through TCL1 and NFκB repressor complex, suggesting the relevance for NFκB as a therapeutic target in CLL.

Original languageEnglish (US)
Pages (from-to)3663-3667
Number of pages5
JournalCell Cycle
Volume8
Issue number22
DOIs
StatePublished - Nov 15 2009
Externally publishedYes

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Epigenomics
B-Lymphocytes
Gene Silencing
Oncogenes
Immunoglobulin M
Leukemia
Transcription Factors
Parturition
Phenotype

Keywords

  • CLL
  • Epigenetics
  • Genetics
  • Methylation
  • TCL1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Chen, S. S., Sherman, M., Hertlein, E., Johnson, A. J., Teitell, M. A., Byrd, J. C., & Plass, C. (2009). Epigenetic alterations in a murine model for chronic lymphocytic leukemia. Cell Cycle, 8(22), 3663-3667. https://doi.org/10.4161/cc.8.22.9957

Epigenetic alterations in a murine model for chronic lymphocytic leukemia. / Chen, Shih Shih; Sherman, Mara; Hertlein, Erin; Johnson, Amy J.; Teitell, Michael A.; Byrd, John C.; Plass, Christoph.

In: Cell Cycle, Vol. 8, No. 22, 15.11.2009, p. 3663-3667.

Research output: Contribution to journalReview article

Chen, SS, Sherman, M, Hertlein, E, Johnson, AJ, Teitell, MA, Byrd, JC & Plass, C 2009, 'Epigenetic alterations in a murine model for chronic lymphocytic leukemia', Cell Cycle, vol. 8, no. 22, pp. 3663-3667. https://doi.org/10.4161/cc.8.22.9957
Chen SS, Sherman M, Hertlein E, Johnson AJ, Teitell MA, Byrd JC et al. Epigenetic alterations in a murine model for chronic lymphocytic leukemia. Cell Cycle. 2009 Nov 15;8(22):3663-3667. https://doi.org/10.4161/cc.8.22.9957
Chen, Shih Shih ; Sherman, Mara ; Hertlein, Erin ; Johnson, Amy J. ; Teitell, Michael A. ; Byrd, John C. ; Plass, Christoph. / Epigenetic alterations in a murine model for chronic lymphocytic leukemia. In: Cell Cycle. 2009 ; Vol. 8, No. 22. pp. 3663-3667.
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