Ontology type: schema:ScholarlyArticle Open Access: True
2015-03-23
AUTHORSS Rodriguez-Perales, R Torres-Ruiz, J Suela, F Acquadro, M C Martin, E Yebra, J C Ramirez, S Alvarez, J C Cigudosa
ABSTRACTWe have identified a new t(1;21)(p32;q22) chromosomal translocation in a MDS/AML patient that results in expression of an aberrant C-terminally truncated RUNX1 protein lacking several regulatory domains. As similar truncated RUNX1 proteins are generated by genetic aberrations including chromosomal translocations and point mutations, we used the t(1;21)(p32;q22) chromosomal translocation as a model to explore whether C-terminally truncated RUNX1 proteins trigger effects similar to those induced by well-characterized leukemogenic RUNX1 fusion genes. In vitro analysis of transduced human hematopoietic/progenitor stem cells showed that truncated RUNX1 proteins increase proliferation and self-renewal and disrupt the differentiation program by interfering with RUNX1b. These effects are similar to but milder than those induced by the RUNX1/ETO fusion protein. GSEA analysis confirmed similar altered gene expression patterns in the truncated RUNX1 and RUNX1/ETO models, with both models showing alterations in genes involved in self-renewal and leukemogenesis, including homeobox genes, primitive erythroid genes and leukemogenic transcription factors. We propose that C-terminally truncated RUNX1 proteins can contribute to leukemogenesis in a similar way to RUNX1 fusion genes but through a milder phenotype. More... »
PAGES125-134
http://scigraph.springernature.com/pub.10.1038/onc.2015.70
DOIhttp://dx.doi.org/10.1038/onc.2015.70
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/25798834
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