Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Molecular and Cellular Biology

Abstract 2077: DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL

Sanghoon Lee, Changhong Yin, Janet Ayello, Carmella van de Ven and Mitchell S. Cairo
Sanghoon Lee
New York Medical College, Valhalla, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Changhong Yin
New York Medical College, Valhalla, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janet Ayello
New York Medical College, Valhalla, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carmella van de Ven
New York Medical College, Valhalla, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitchell S. Cairo
New York Medical College, Valhalla, NY.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2015-2077 Published August 2015
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

BACKGROUND:

Burkitt Lymphoma (BL) is the most common histological subtype of childhood and adolescent Non Hodgkin Lymphoma (Cairo et al, Blood 2007; Miles/Cairo, BJH 2012). Pediatric patients with BL with a chromosome 13q deletion, particularly 13q14.3, had significantly poorer outcome and inferior overall survival despite aggressive short, intensive multi-agent chemotherapy (Poirel/Cairo et al, Leukemia 2009; Nelson/Cairo/Sanger et al, BJH 2009). Deleted in Lymphocytic Leukemia 1 (DLEU1) is a BL classifier gene in the 13q14.3 (Dave et al, NEJM 2006) and it has been implicated in regulating programmed cell death in patients. Sequence-specific Transcription Activator-Like Effector Nucleases (TALENs) have been developed for precision targeted genome editing in in vitro and in vivo (Sander et al, Nat Bio 2011).

OBJECTIVES:

We hypothesize that DLEU1 may act as a tumor suppressor gene and therefore investigated whether DLEU1 expression results in changes in gene expression profiles, cell viability, apoptosis induced by chemoimmunotherapy regimens in DLEU1 knockout and/or DLEU1 overexpressing Raji BL cells.

METHODS:

TALEN-mediated DLEU1 knockout (DLEU1-KO) and DLEU1 overexpressing Raji BL cells (DLEU1-OE) were treated with Rituximab (RTX) and/or Cyclophosphamide (CTX). MTS, Caspase assay, qRT-PCR, western blot, and gene expression profiling using Affymetrix HG-133+ 2.0 arrays were performed.

RESULTS:

A significant decrease of apoptosis in DLEU1-KO (32.5±11.8%, p<.05) and a significant increase in DLEU1-OE (9.7±5.5%, p<.05) were observed vs control. A total 2,501 differentially expressed genes were identified by gene expression profiling (>2 fold, p<.05) and 79.8% of genes including signaling pathways and anti-apoptosis related genes including ATK1, ikBa and Bcl-2 were upregulated in DLEU1-KO.. There was a significant decrease in apoptosis with RTX, CTX and in combination (0.85±0.05, 0.76±0.09, and 0.65±0.17, p<.05, respectively) in DLEU1-KO whereas a significant increase with RTX (11.5%, p<.05), CTX (13.9%, p<.05) in DLEU1-OE. A significant increase in cell proliferation was observed with RTX, CTX and combination (1.14±0.06, 1.1±0.06, and 1.09±0.02, p<.05) in DLEU1-KO whereas a significant decrease with RTX, CTX and in combination (0.92±0.01, 0.89±0.04, and 0.87±0.04, p<.05, respectively) in DLEU1-OE vs control.

CONCLUSIONS:

We demonstrate that 1) DLEU1 knockout resulted in significant changes of ikBa and Akt1 expression, inhibition of apoptosis and increase of viability in RTX and CTX treatment; 2) DLEU1 overexpression significantly inhibited cell viability and increased apoptosis in RTX and CTX treatment. We hypothesize that deletion of DLEU1 in pediatric BL may in part result in chemotherapy resistance secondarily to a loss of a tumor suppressor gene.

Citation Format: Sanghoon Lee, Changhong Yin, Janet Ayello, Carmella van de Ven, Mitchell S. Cairo. DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2077. doi:10.1158/1538-7445.AM2015-2077

  • ©2015 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 75 (15 Supplement)
August 2015
Volume 75, Issue 15 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract 2077: DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 2077: DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL
Sanghoon Lee, Changhong Yin, Janet Ayello, Carmella van de Ven and Mitchell S. Cairo
Cancer Res August 1 2015 (75) (15 Supplement) 2077; DOI: 10.1158/1538-7445.AM2015-2077

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 2077: DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL
Sanghoon Lee, Changhong Yin, Janet Ayello, Carmella van de Ven and Mitchell S. Cairo
Cancer Res August 1 2015 (75) (15 Supplement) 2077; DOI: 10.1158/1538-7445.AM2015-2077
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Molecular and Cellular Biology

  • Abstract RAOS15-03: Pancreatic tumor stroma as a therapeutic target
  • Abstract DDT02-01: Inhibition of the AAA-ATPase p97 with the first in class inhibitor CB-5083 as a novel approach to treat cancer
  • Abstract LB-298: The multiple-myeloma associated snoRNA, ACA11 increases oxidative stress and cell proliferation
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013
  • Abstract LB-001: Impact of direct physician engagement with racial/ethnic minorities for oncology clinical trial access and accrual model
  • Abstract LB-107: EV-TRACK: transparent reporting and centralizing knowledge of extracellular vesicles to support the validation of extracellular vesicle biomarkers in cancer research
Show more 3

Poster Presentations - Oncogenes and Tumor Suppressors 2

  • Abstract 4466: The key role of Abi1 loss in dysregulating cell-cell adhesion during prostate cancer tumorigenesis
  • Abstract 4467: ETV6 is a tumor suppressor regulated by EGFR-miR-96 pathway in prostate cancer
  • Abstract 4455: Identification of novel oncogene, copine-7 (CPNE7), in colorectal cancer
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement