Comprehensive Genomic Screens Reveal Multiple Modes of Action of the PLZF-RAR-α Oncoprotein

The t(11;17)(q23;q21) translocation is associated with a retinoic acid-insensitive form of acute promyelocytic leukemia (APL) involving the production of reciprocal fusion proteins PLZF-RARα and RARα-PLZF. These proteins mediate malignant transformation by binding to and dysregulating RARα/RXR and P...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2008-11, Vol.112 (11), p.686-686
Main Authors: Rice, Kim L., Hormaeche, Itsaso, McConnell, Melanie J., Doulatov, Sergei, Flatow, Jared, Grimwade, David, Mills, Ken I, Dick, John E., Licht, Jonathan D.
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The t(11;17)(q23;q21) translocation is associated with a retinoic acid-insensitive form of acute promyelocytic leukemia (APL) involving the production of reciprocal fusion proteins PLZF-RARα and RARα-PLZF. These proteins mediate malignant transformation by binding to and dysregulating RARα/RXR and PLZF target genes, respectively. In order to investigate the molecular basis of PLZF-RARα induced leukemia, we performed a genome wide screen for PLZF-RARα direct target genes using a gain of function model in which PLZF-RARα was expressed in human U937 leukemia cells. Chromatin from U937/PLZF-RARα cells was immunoprecipitated using PLZF antibodies, amplified by ligation-mediated PCR and biological triplicates were hybridized to NimbleGen 2.7kB promoter arrays, which represent 24,659 human promoters. We identified 4916 genes directly bound by PLZF-RARα (2/3 biological replicates, FDR
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V112.11.686.686