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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cells, Cultured
-
Chromosome Aberrations*
-
Chromosomes, Human, Pair 21 / genetics
-
Chromosomes, Human, Pair 8 / genetics
-
Core Binding Factor Alpha 2 Subunit / genetics
-
Fluorescent Antibody Technique
-
Gene Expression Regulation*
-
Hematopoietic Stem Cells / cytology
-
Hematopoietic Stem Cells / metabolism*
-
Humans
-
In Situ Hybridization, Fluorescence
-
Oncogene Proteins, Fusion / genetics*
-
Proto-Oncogene Proteins / genetics
-
RNA, Messenger / genetics
-
RUNX1 Translocation Partner 1 Protein
-
Real-Time Polymerase Chain Reaction
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction
-
Transcription Factors / genetics
-
Translocation, Genetic / genetics*
-
Wnt Proteins / genetics*
-
beta Catenin / genetics*
Substances
-
Core Binding Factor Alpha 2 Subunit
-
Oncogene Proteins, Fusion
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
RUNX1 Translocation Partner 1 Protein
-
RUNX1 protein, human
-
RUNX1T1 protein, human
-
Transcription Factors
-
Wnt Proteins
-
beta Catenin