The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential mechanism of chemoimmunotherapy resistance in BL
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Sanghoon Lee1,2,*, Wen Luo1,*, Tishi Shah1, Changhong Yin1, Timmy O’Connell1,3, Tae-Hoon Chung4, Sherrie L. Perkins5, Rodney R. Miles5, Janet Ayello1, Erin Morris1, Lauren Harrison1, Carmella van de Ven1, Mitchell S. Cairo1,2,3,6,7
1Departments of Pediatrics, New York Medical College, Valhalla, New York, USA
2Departments of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA
3Departments of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA
4Cancer Science Institute of Singapore, National University of Singapore, Singapore
5Department of Pathology and ARUP Laboratories, University of Utah, Salt Lake City, Utah, USA
6Departments of Pathology, New York Medical College, Valhalla, New York, USA
7Departments of Medicine, New York Medical College, Valhalla, New York, USA
*First and primary co-authors
Mitchell S. Cairo, email: email@example.com
Keywords: DLEU1, tumor suppressor, chemoimmunotherapy, genome editing, B-NHL
Received: November 17, 2016 Accepted: February 12, 2017 Published: February 24, 2017
Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines. Furthermore, NSG mice xenografted with DLEU1 knockdown BL cells had significantly shortened survival (p < 0.05 and p < 0.005), whereas those xenografted with DLEU1 overexpressing BL cells had significantly improved survival (p < 0.05 and p < 0.0001), following treatment with rituximab and/or cyclophosphamide. These data suggest that DLEU1 may in part function as a tumor suppressor gene and confer chemoimmunotherapy resistance in children and adolescents with BL.
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