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

PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying -mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by and , in the aberrant self-renewal. Indeed, as well as rendered those cells immortalized through upregulation of also led to immortalization without differentiation block, while depletion of suppressed clonogenicity in cells immortalized by 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 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 APL.