Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 182, Issue 4, Pages 1092-1098Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.12.013
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Funding
- Deutsche Krebshilfe (Network Molecular Mechanisms of Malignant Lymphoma)
- BMBF Medical Systems biology HaematoSys [BMBF-FKZ 0315452]
- Deutsche Forschungsgemeinschaft [GRK1034, FOR942]
- Leukaemia and Lymphoma Research Fund
- Kubeschka-Stricker-Wirth-Stiftung at the Georg-August-Universitat
- German Academic Exchange Service fellowship
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Burkitt's Lymphoma (BL) is a highly malignant, aggressive non-Hodgkin's lymphoma derived from germinal center B cells. Recently, global gene expression profiling of patient samples Led to a molecular definition of BL with lymphocyte enhancer binding factor 1 (LEF1) as a signature gene. Herein, we report the expression of nucleic LEF1 in 15 of 18 patients with BL and the identification of LEF1 target genes. Germinal center B cells were devoid of detectable nuclear LEF1 expression, as were mantle cell lymphoma (0 of 5), marginal zone lymphoma (0 of 6), follicular lymphoma (0 of 12), and diffuse large B-cell lymphoma (1 of 31). Whole-genome gene expression profiling after transient knockdown of LEF1 in BL cell Lines identified new LEF1 target genes; these LEF1 targets are enriched with genes associated with cancers. The expression of LEF1 and LEF1-regulated genes in primary BL suggests that LEF1 is not only aberrantly expressed but also transcriptionally active. This study supports a functionally important role for LEF1 and its target genes in BLs.
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