In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3' regulatory region induces MYC expression at the immature stage of B cell development

Yi Yan; Sung Sup Park; Siegfried Janz; Laurel A Eckhardt

doi:10.1002/gcc.20480

Back

In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3' regulatory region induces MYC expression at the immature stage of B cell development

Journal article

Peer reviewed

In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3' regulatory region induces MYC expression at the immature stage of B cell development

Yi Yan, Sung Sup Park, Siegfried Janz and Laurel A Eckhardt

Genes chromosomes & cancer, Vol.46(10), pp.950-959

10/2007

DOI: 10.1002/gcc.20480

PMCID: PMC2742353

PMID: 17639584

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/2742353View

Open Access

Abstract

Reciprocal translocations involving the immunoglobulin loci and the cellular oncogene MYC are hallmark mutations of the human postgerminal center B cell neoplasm, Burkitt's lymphoma. They are occasionally found in other B cell lymphomas, as well. Translocations involving the heavy chain locus (IGH) place the MYC gene either in cis with both the intronic enhancer Emu and the IGH 3' regulatory region (3'RR) or in cis with only the 3'RR. The result is deregulated MYC expression. Recent studies have led to some controversy as to when, during B lymphocyte development, IGH/MYC chromosome translocations take place. A related issue, relevant not only to lymphoma development but also to normal controls on IGH gene expression, is the stage, during B lymphocyte development, at which the 3'RR is capable of activating MYC expression. We have developed mice transgenic for a human MYC (hMYC) gene under control of the four core enhancers from the mouse Igh 3'RR. Unlike other transgenic mouse models where premature and inappropriate MYC expression disrupts normal B cell development, the hMYC transgene in these studies carries a mutation that prohibits MYC protein synthesis. As a result, hMYC expression can be analyzed in all of the normal B cell compartments. Our data show that hMYC is expressed almost exclusively in B-lineage cells and is induced to high levels as soon as bone marrow cells reach the immature B cell stage.

Spleen

Blotting, Southern

Promoter Regions, Genetic

Translocation, Genetic

B-Lymphocytes - cytology

Humans

Regulatory Sequences, Nucleic Acid

Cells, Cultured

Gene Expression Regulation, Neoplastic

3' Untranslated Regions - genetics

Mice, Transgenic

Reverse Transcriptase Polymerase Chain Reaction

Proto-Oncogene Proteins c-myc - metabolism

Animals

Flow Cytometry

Burkitt Lymphoma - immunology

Lipopolysaccharides - pharmacology

Burkitt Lymphoma - genetics

Mice

Proto-Oncogene Proteins c-myc - genetics

B-Lymphocytes - metabolism

Bone Marrow Cells - metabolism

Immunoglobulin Heavy Chains - genetics

Details

Title: Subtitle: In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3' regulatory region induces MYC expression at the immature stage of B cell development
Creators: Yi Yan - Department of Biological Sciences, Hunter College and Graduate Center of the City University of New York, New York, NY, USA
Sung Sup Park
Siegfried Janz
Laurel A Eckhardt
Resource Type: Journal article
Publication Details: Genes chromosomes & cancer, Vol.46(10), pp.950-959
DOI: 10.1002/gcc.20480
PMID: 17639584
PMCID: PMC2742353
NLM abbreviation: Genes Chromosomes Cancer
ISSN: 1045-2257
eISSN: 1098-2264
Grant note: AI30653 / NIAID NIH HHS RR-0307 / NCRR NIH HHS R01 AI030653-17 / NIAID NIH HHS R01 AI030653 / NIAID NIH HHS
Language: English
Date published: 10/2007
Academic Unit: Pathology
Record Identifier: 9984083842502771

Metrics

20 Record Views

14 Times Cited - Web of Science