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

Molecular Cancer
Chi Keung ChengMargaret H L Ng

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.

References

Dec 23, 2010·Future Oncology·Etienne De BraekeleerMarc De Braekeleer
Mar 30, 2011·Journal of Cellular Biochemistry·Elena N MarkovaSergey V Razin
Feb 24, 2016·PloS One·Milka MartinezSoraya E Gutierrez
Feb 10, 2017·Blood·Raman SoodPaul Liu

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Citations

Aug 5, 2020·Journal of Experimental & Clinical Cancer Research : CR·Ting WangYujun Hao
Dec 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shujing ZhangHongmin Liu
Aug 28, 2021·Genes·Amarni L ThomasJulia A Horsfield

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Methods Mentioned

BETA
MDS
RNA-Seq
PCR
ChIP-seq
chromosomal aberrations

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