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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Letter to the Editor

RUNX1 upregulation via disruption of long-range transcriptional control by a novel t(5;21)(q13;q22) translocation in acute myeloid leukemia

Authors: Chi-Keung Cheng, Terry H. Y. Wong, Thomas S. K. Wan, Angela Z. Wang, Natalie P. H. Chan, Nelson C. N. Chan, Chi-Kong Li, Margaret H. L. Ng

Published in: Molecular Cancer | Issue 1/2018

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Abstract

RUNX1 encodes a Runt-related transcription factor that is critical for hematopoiesis. In this study, through a combinatorial molecular approach, we characterized a novel t(5;21)(q13;q22) translocation involving RUNX1 that was acquired during the progression of myelodysplastic syndrome to acute myeloid leukemia (AML) in a pediatric patient. We found that this translocation did not generate RUNX1 fusion but aberrantly upregulated RUNX1. This upregulation was attributed to the disruption of long-range chromatin interactions between the RUNX1 P2 promoter and a silencer in the first intron of the gene. Characterization of the silencer revealed a role of SNAG repressors and their corepressor LSD1/KDM1A in mediating the effect. Our findings suggest that chromosomal rearrangements may activate RUNX1 by perturbing its transcriptional control to contribute to AML pathogenesis, in keeping with an emerging oncogenic role of RUNX1 in leukemia.
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Metadata
Title
RUNX1 upregulation via disruption of long-range transcriptional control by a novel t(5;21)(q13;q22) translocation in acute myeloid leukemia
Authors
Chi-Keung Cheng
Terry H. Y. Wong
Thomas S. K. Wan
Angela Z. Wang
Natalie P. H. Chan
Nelson C. N. Chan
Chi-Kong Li
Margaret H. L. Ng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0881-2

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