Wnt signaling induces transcription, spatial proximity, and translocation of fusion gene partners in human hematopoietic cells.
Blood
; 126(15): 1785-9, 2015 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-26333776
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/ß-catenin signaling increases the expression of ETO and RUNX1 genes in human hematopoietic progenitors. We found that ß-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/ß-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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Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
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Células-Tronco Hematopoéticas
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Proteínas de Fusão Oncogênica
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Regulação da Expressão Gênica
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Aberrações Cromossômicas
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Proteínas Wnt
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Beta Catenina
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article