CircR-looping the leukemic translocations: The cause of MLL translocations explained

Conn et al. 1 Conn V.M. Gabryelska M. Toubia J. Kirk K. Gantley L. Powell J.A. Cildir G. Marri S. Liu R. Stringer B.W. et al. Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia. Cancer Cell. 2023; 41https://doi.org/10.1016/j.ccell.2023.05.002 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar identify circular RNAs (circRNAs) derived from mixed lineage leukemia (MLL) breakpoint cluster regions, demonstrating a causal role of circRNAs in MLL translocations. CircRNAs:DNA hybrids (circR-loops) trigger RNA polymerase pausing, driving oncogenic gene fusions via endogenous RNA-directed DNA damage. Conn et al. 1 Conn V.M. Gabryelska M. Toubia J. Kirk K. Gantley L. Powell J.A. Cildir G. Marri S. Liu R. Stringer B.W. et al. Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia. Cancer Cell. 2023; 41https://doi.org/10.1016/j.ccell.2023.05.002 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar identify circular RNAs (circRNAs) derived from mixed lineage leukemia (MLL) breakpoint cluster regions, demonstrating a causal role of circRNAs in MLL translocations. CircRNAs:DNA hybrids (circR-loops) trigger RNA polymerase pausing, driving oncogenic gene fusions via endogenous RNA-directed DNA damage. Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemiaConn et al.Cancer CellJune 8, 2023In BriefConn et al. identify circular RNA:DNA interactions concentrated within the MLL recombinome, commonly translocated in acute myeloid leukemia. Both in vitro and in vivo experiments demonstrate that endogenous circular RNAs inhibit the proteasome, promote DNA double-stranded breaks, reorganize chromatin, and promote oncogenic gene translocations which drive leukemia. Full-Text PDF