Wnt signaling induces transcription, spatial proximity, and translocation of fusion gene partners in human hematopoietic cells
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Date
2015-10
Profesor/a GuÃa
Facultad/escuela
Idioma
en
Journal Title
Journal ISSN
Volume Title
Publisher
American Society of Hematology
Nombre de Curso
item.page.dc.rights
Atribución 4.0 Internacional (CC BY 4.0)
item.page.dc.rights
https://creativecommons.org/licenses/by/4.0/deed.es
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. © 2015 by The American Society of Hematology.
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Indexación: Scopus
Keywords
Mutation, Acute Myeloid Leukemia, Transcription Factor RUNX1
Citation
DOI
10.1182/blood-2015-04-638494