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JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115466 | GEO | 2018/06/18

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC6028512 | biostudies-literature

JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [ChIP-Seq]

Project description:A substantial subset of patients with T-cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumb 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 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 shRNA knockdown leads to apoptosis. Mechanistically, JDP2 regulates pro-survival 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.

2018-06-18 | GSE115465 | GEO

JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [RNA-Seq]

2018-06-18 | GSE115464 | GEO

JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia

Project description:JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia

| PRJNA475108 | ENA

JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [RNA-Seq]

Project description:JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [RNA-Seq]

| PRJNA475112 | ENA

JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [ChIP-Seq]

Project description:JDP2 - an Oncogenic bZIP Transcription Factor in T-cell Acute Lymphoblastic Leukemia [ChIP-Seq]

| PRJNA475115 | ENA

Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-05-17 | E-GEOD-74312 | biostudies-arrayexpress

Acute lymphoblastic leukemia

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Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-05-17 | GSE74312 | GEO

Oncogenic ZEB2 activation drives sensitivity towards LSD1 inhibition in T-cell acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-03 | GSE83128 | GEO

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