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

Blood
Giorgia D UgarteGiancarlo V De Ferrari

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.

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Citations

Nov 19, 2015·Journal of Cellular Physiology·Matías A MedinaGiancarlo V De Ferrari
Jan 19, 2018·International Journal of Molecular Sciences·Silje JohansenØystein Bruserud
Jun 24, 2020·Journal of Leukocyte Biology·Sheila C Soares-LimaFlávia R G Carneiro
Nov 11, 2019·Cells·Alicja M GruszkaMyriam Alcalay
Apr 24, 2020·Stem Cell Research & Therapy·Linqing ZouGuoqi Song
Jan 25, 2017·Neural Plasticity·Eduardo Pérez-PalmaGiancarlo V De Ferrari
Jan 19, 2019·International Journal of Molecular Sciences·Emiel van der Kouwe, Philipp Bernhard Staber
Aug 3, 2019·Journal of Experimental & Clinical Cancer Research : CR·Qingyuan LiSide Liu
Jan 9, 2021·Journal of Cellular and Molecular Medicine·Yifeng DaiTiansheng Zeng
Oct 19, 2021·Frontiers in Cell and Developmental Biology·Abdulrahman IbrahimAhmed Gamal Ibrahim

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