UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia

Mansour, MR; He, S; Li, Z; Lobbardi, R; Abraham, BJ; Hug, C; Rahman, S; ... Look, TA; + view all (2018) JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. Journal of Experimental Medicine , 215 (7) , Article 1929. 10.1084/jem.20170484. Green open access

[img]
Preview
Text
JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia.pdf - ["content_typename_Published version" not defined]

Download (3MB) | Preview

Abstract

A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumbs to their disease. JDP2 encodes a bZIP protein that has been implicated as a T-ALL oncogene from insertional mutagenesis studies in mice, but its role in human T-ALL pathogenesis has remained obscure. Here we show that JDP2 is aberrantly expressed in a subset of T-ALL patients and is associated with poor survival. JDP2 is required for T-ALL cell survival, as its depletion by short hairpin RNA knockdown leads to apoptosis. Mechanistically, JDP2 regulates prosurvival signaling through direct transcriptional regulation of MCL1. Furthermore, JDP2 is one of few oncogenes capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from rag2:jdp2 transgenic zebrafish express high levels of mcl1 and demonstrate resistance to steroids in vivo. These studies establish JDP2 as a novel oncogene in high-risk T-ALL and implicate overexpression of MCL1 as a mechanism of steroid resistance in JDP2-overexpressing cells.

Type: Article
Title: JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20170484
Publisher version: https://doi.org/10.1084/jem.20170484
Language: English
Additional information: Copyright © 2018 Mansour et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/10050095
Downloads since deposit
30Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item