Oncotarget

Research Papers:

The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential mechanism of chemoimmunotherapy resistance in BL

Sanghoon Lee, Wen Luo, Tishi Shah, Changhong Yin, Timmy O’Connell, Tae-Hoon Chung, Sherrie L. Perkins, Rodney R. Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella van de Ven and Mitchell S. Cairo _

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Oncotarget. 2017; 8:27839-27853. https://doi.org/10.18632/oncotarget.15711

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Abstract

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

Correspondence to:

Mitchell S. Cairo, email: mitchell_cairo@nymc.edu

Keywords: DLEU1, tumor suppressor, chemoimmunotherapy, genome editing, B-NHL

Received: November 17, 2016     Accepted: February 12, 2017     Published: February 24, 2017

ABSTRACT

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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