Unknown

Dataset Information

0

Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced Leukemogenesis.


ABSTRACT: PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal. Indeed, PLZF-RARA as well as Plzf rendered those cells immortalized through upregulation of Eya2. Eya2 also led to immortalization without differentiation block, while depletion of Eya2 suppressed clonogenicity in cells immortalized by PLZF-RARA without influence on differentiation and apoptosis. Interestingly, cancer outlier profile analysis of human samples of acute myeloid leukemia (AML) in The Cancer Genome Atlas (TCGA) revealed a subtype of AML that strongly expressed EYA2 In addition, gene set enrichment analysis of human AML samples, including TCGA data, showed that this subtype of AML was more closely associated with the properties of leukemic stem cells in its gene expression signature than other AMLs. Therefore, EYA2 may be a target for molecular therapy in this subtype of AML, including PLZF-RARA APL.

SUBMITTER: Ono R 

PROVIDER: S-EPMC5472835 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Eya2, a Target Activated by Plzf, Is Critical for <i>PLZF-RARA</i>-Induced Leukemogenesis.

Ono Ryoichi R   Masuya Masahiro M   Ishii Satomi S   Katayama Naoyuki N   Nosaka Tetsuya T  

Molecular and cellular biology 20170615 13


PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the <i>PLZF-RARA</i> fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying <i>PLZF</i>-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with <i>Plzf</i> was performed, which revealed the i  ...[more]

Similar Datasets

| S-EPMC3176768 | biostudies-literature
| S-EPMC3619279 | biostudies-literature
| S-EPMC5355061 | biostudies-literature
| S-EPMC5341809 | biostudies-literature
2009-12-05 | E-GEOD-18476 | biostudies-arrayexpress
2009-11-30 | GSE18476 | GEO
| S-EPMC2254548 | biostudies-literature
| S-EPMC6820555 | biostudies-literature
| S-EPMC2214769 | biostudies-literature
| S-EPMC5795782 | biostudies-literature