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

• Published in: The Journal of experimental medicine 2018-07, Vol.215 (7), p.1929-1945
• Main Authors: Mansour, Marc R, He, Shuning, Li, Zhaodong, Lobbardi, Riadh, Abraham, Brian J, Hug, Clemens, Rahman, Sunniyat, Leon, Theresa E, Kuang, You-Yi, Zimmerman, Mark W, Blonquist, Traci, Gjini, Evisa, Gutierrez, Alejandro, Tang, Qin, Garcia-Perez, Laura, Pike-Overzet, Karin, Anders, Lars, Berezovskaya, Alla, Zhou, Yi, Zon, Leonard I, Neuberg, Donna, Fielding, Adele K, Staal, Frank J T, Langenau, David M, Sanda, Takaomi, Young, Richard A, Look, A Thomas
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Animals; Apoptosis; Apoptosis - drug effects; Base Sequence; Cell Proliferation - drug effects; Cell survival; Cell Survival - drug effects; Child, Preschool; Danio rerio; Dexamethasone - pharmacology; Disease Models, Animal; Enhancer Elements, Genetic - genetics; Gene Expression Regulation, Leukemic - drug effects; Gene regulation; Glucocorticoids - pharmacology; Humans; In vivo methods and tests; Infant; Insertional mutagenesis; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Mcl-1 protein; Mice; Mutagenesis, Insertional - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Neoplasm Transplantation; Oncogenes; Pathogenesis; Patients; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Protein Binding - drug effects; Proteins; Proto-Oncogene Proteins c-myc - metabolism; RAG2 protein; Repressor Proteins - genetics; Repressor Proteins - metabolism; Response Elements - genetics; Ribonucleic acid; RNA; Steroid hormones; Steroids; Survival; Thymocytes; Thymocytes - drug effects; Thymocytes - metabolism; Transcription factors; Treatment Outcome; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20170484

A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumbs to their disease. 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 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 Furthermore, is one of few oncogenes capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from transgenic zebrafish express high levels of and demonstrate resistance to steroids in vivo. These studies establish as a novel oncogene in high-risk T-ALL and implicate overexpression of as a mechanism of steroid resistance in -overexpressing cells.