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

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1785-1789
Number of pages5
JournalBlood
Volume126
Issue number15
DOIs
Publication statusPublished - 8 Oct 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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