How RNA molecules influence the development of aggressive leukemia

Researchers at the University of Veterinary Medicine Vienna, in collaboration with other institutions, have developed a new method to identify RNA molecules involved in aggressive leukemia. This method, called bicon-seq, reveals which RNAs are associated with biomolecular condensates—dynamic structures in cells where biomolecules interact to influence gene activity.

The study focused on the NUP98::KDM5A oncogenic condensates, which are crucial for activating leukemia-relevant genes in aggressive forms of acute myeloid leukemia (AML). The analysis identified the long noncoding RNA Gas5 as an important regulator of these condensates. Gas5 is highly expressed in AML cells and co-localizes with the NUP98::KDM5A oncoprotein within condensates, playing a role in leukemia cell proliferation.

When Gas5 was downregulated, changes in gene activity were observed, particularly affecting genes involved in differentiation and programmed cell death. This research highlights the significance of noncoding RNAs, such as Gas5, in the function of fusion oncoproteins and provides a new experimental approach for studying their roles in disease.