PUBLICATION
JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia
- Authors
- Mansour, M.R., He, S., Li, Z., Lobbardi, R., Abraham, B.J., Hug, C., Rahman, S., Leon, T.E., Kuang, Y.Y., Zimmerman, M.W., Blonquist, T., Gjini, E., Gutierrez, A., Tang, Q., Garcia-Perez, L., Pike-Overzet, K., Anders, L., Berezovskaya, A., Zhou, Y., Zon, L.I., Neuberg, D., Fielding, A.K., Staal, F.J.T., Langenau, D.M., Sanda, T., Young, R.A., Look, A.T.
- ID
- ZDB-PUB-180627-3
- Date
- 2018
- Source
- The Journal of experimental medicine 215(7): 1929-1945 (Journal)
- Registered Authors
- Berezovskaya, Alla, Gjini, Evisa, Gutierrez, Alejandro, He, Shuning, Langenau, David, Li, Zhaodong, Look, A. Thomas, Mansour, Marc, Sanda, Takaomi, Tang, Qin, Zhou, Yi, Zimmerman, Mark, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Oncogenes*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Glucocorticoids/pharmacology
- Proto-Oncogene Proteins c-myc/metabolism
- Apoptosis/drug effects
- Zebrafish
- Protein Binding/drug effects
- Disease Models, Animal
- Infant
- Treatment Outcome
- Cell Survival/drug effects
- Thymocytes/drug effects
- Thymocytes/metabolism
- Enhancer Elements, Genetic/genetics
- Gene Expression Regulation, Leukemic/drug effects
- Dexamethasone/pharmacology
- Mice
- Child, Preschool
- Neoplasm Transplantation
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics*
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology
- Humans
- Base Sequence
- Mutagenesis, Insertional/genetics
- Repressor Proteins/genetics*
- Repressor Proteins/metabolism
- Myeloid Cell Leukemia Sequence 1 Protein/metabolism
- Animals
- Response Elements/genetics
- Cell Proliferation/drug effects
- PubMed
- 29941549 Full text @ J. Exp. Med.
Citation
Mansour, M.R., He, S., Li, Z., Lobbardi, R., Abraham, B.J., Hug, C., Rahman, S., Leon, T.E., Kuang, Y.Y., Zimmerman, M.W., Blonquist, T., Gjini, E., Gutierrez, A., Tang, Q., Garcia-Perez, L., Pike-Overzet, K., Anders, L., Berezovskaya, A., Zhou, Y., Zon, L.I., Neuberg, D., Fielding, A.K., Staal, F.J.T., Langenau, D.M., Sanda, T., Young, R.A., Look, A.T. (2018) JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. The Journal of experimental medicine. 215(7):1929-1945.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping