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

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 RUN

SUBMITTER: Cheng CK 

PROVIDER: S-EPMC6116564 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature