RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. The t(8;21) translocation is found in 30%-40% of cases of acute myeloid leukemia (AML). Recent whole-exome sequencing also reveals mutations and deletions of RUNX1 in some solid tumors.
Researchers from Jilin University, China describe a RUNX1-intragenic long noncoding RNA ROPNR that is transcribed as unspliced transcript from an upstream overlapping promoter. ROPNR was upregulated in AML samples and in response to Ara-C treatment in vitro. ROPNR utilizes its 3′-terminal fragment to directly interact with the RUNX1 promoter and enhancers and participates in the orchestration of an intrachromosomal loop. The 3′ region of ROPNR also participates in long-range interchromosomal interactions with chromatin regions that are involved in multiple RUNX1 translocations. These data suggest that ROPNR noncoding RNA may function as a previously unidentified candidate component that is involved in chromosomal translocation in hematopoietic malignancies.
- Wang H, Li W, Guo R, Sun J, Cui J, Wang G, Hoffman AR, Hu JF. (2014) An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies. Int J Cancer [Epub ahead of print]. [abstract]