Wnt signaling induces transcription, spatial proximity, and translocation of fusion gene partners in human hematopoietic cells

Giorgia D. Ugarte, Macarena F. Vargas, Matías A. Medina, Pablo León, David Necuñir, Alvaro A. Elorza, Soraya E. Gutiérrez, Randall T. Moon, Alejandra Loyola, Giancarlo V. De Ferrari

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

18 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)1785-1789
Número de páginas5
PublicaciónBlood
Volumen126
N.º15
DOI
EstadoPublicada - 8 oct 2015

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Inmunología
  • Hematología
  • Biología celular

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