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• W2014862318 abstract "Erythropoietin-producing hepatoma-amplified sequence (Eph) receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, function as a unique signaling system triggered by cell-to-cell interaction and have been shown to mediate neurodevelopmental processes. In addition, recent studies showed deregulation of some of Eph / ephrin genes in human malignancies, suggesting the involvement of this signaling pathway in tumorigenesis. The ALL1 (also termed MLL ) gene on human chromosome 11q23 was isolated by virtue of its involvement in recurrent chromosome translocations associated with acute leukemias with poor prognosis. The translocations fuse ALL1 to any of >50 partner genes and result in production of chimeric proteins composed of the ALL1 N terminus and the C terminus of the partner protein. The most common translocations in ALL1 -associated leukemias are t(4;11) and t(9;11), which generate ALL1/AF4 and ALL1/AF9 fusion protein, respectively. In the present study, we sought to determine whether ALL1 fusion proteins are involved in regulation of Eph / ephrin genes. Screening of K562 cells producing recombinant ALL1/AF4 or ALL1/AF9 fusion protein revealed transcriptional up-regulation of the EphA7 . Consistent with this finding, siRNA-mediated suppression of ALL1/AF4 in SEMK2 cells carrying the t(4;11) chromosome translocation resulted in down-regulation of EphA7 . ChIP analysis demonstrated the occupancy of tagged ALL1 fusion proteins on the EphA7 promoter, pointing to EphA7 as a direct target of the formers. Further studies demonstrate that EphA7 up-regulation is accompanied by ERK phosphorylation. Finally, we show apoptotic cell death, specific for leukemic cells carrying the t(4;11) chromosome translocation, after treatment of the cells with an ERK phosphorylation blocker." @default.
• W2014862318 created "2016-06-24" @default.
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• W2014862318 date "2007-09-04" @default.
• W2014862318 modified "2023-10-18" @default.
• W2014862318 title "ALL1 fusion proteins induce deregulation of <i>EphA7</i> and ERK phosphorylation in human acute leukemias" @default.
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• W2014862318 doi "https://doi.org/10.1073/pnas.0703211104" @default.
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