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

Autor: Cheng CK; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Wong THY; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Wan TSK; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Wang AZ; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Chan NPH; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Chan NCN; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Li CK; Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong., Ng MHL; Blood Cancer Cytogenetics and Genomics Laboratory, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. margaretng@cuhk.edu.hk.; State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Shatin, Hong Kong. margaretng@cuhk.edu.hk.
Jazyk: angličtina
Zdroj: Molecular cancer [Mol Cancer] 2018 Aug 29; Vol. 17 (1), pp. 133. Date of Electronic Publication: 2018 Aug 29.
DOI: 10.1186/s12943-018-0881-2
Abstrakt: 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.
Databáze: MEDLINE
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