Format

Send to

Choose Destination
J Exp Med. 2018 Jul 2;215(7):1929-1945. doi: 10.1084/jem.20170484. Epub 2018 Jun 25.

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

Author information

1
Department of Haematology, University College London Cancer Institute, London, England, UK m.mansour@ucl.ac.uk.
2
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
3
Molecular Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA.
4
Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA.
5
Whitehead Institute for Biomedical Research, Cambridge, MA.
6
Department of Haematology, University College London Cancer Institute, London, England, UK.
7
Heilongjiang River Fisheries Research Institute of Chinese Academy of Fishery Sciences, Harbin, China.
8
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
9
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA.
10
Department of Immunohematology, Leiden University Medical Center, Leiden, Netherlands.
11
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
12
Department of Medicine, Yong Loo Lin School of Medicine, Singapore.
13
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
14
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA thomas_look@dfci.harvard.edu.

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.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center