Examinando por Autor "Vargas, Macarena F."

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    Wnt signaling induces transcription, spatial proximity, and translocation of fusion gene partners in human hematopoietic cells
    (American Society of Hematology, 2015-10) Ugarte, Giorgia D.; Vargas, Macarena F.; Medina, Matías A.; León, Pablo; Necuñir, David; Elorza, Alvaro A.; Gutiérrez, Soraya E.; Moon, Randall T.; Loyola, Alejandra; De Ferrari, Giancarlo V.
    Chromosomal translocations are frequently associated with a wide variety of cancers, particularly hematologic malignancies. A recurrent chromosomal abnormality in acute myeloid leukemia is the reciprocal translocation t(8;21) that fuses RUNX1 and ETO genes. We report here that Wnt/β-catenin signaling increases the expression of ETO and RUNX1 genes in human hematopoietic progenitors. We found that β-catenin is rapidly recruited into RNA polymerase II transcription factories (RNAPII-Ser5) and that ETO and RUNX1 genes are brought into close spatial proximity upon Wnt3a induction. Notably, long-term treatment of cells with Wnt3a induces the generation a frequent RUNX1-ETO translocation event. Thus, Wnt/β-catenin signaling induces transcription and translocation of RUNX1 and ETO fusion gene partners, opening a novel window to understand the onset/development of leukemia. © 2015 by The American Society of Hematology.