Liquid-liquid phase separation is a process cells use to organize proteins and other molecules without binding them within a membrane. Scientists at St. Jude are studying how this process is involved in pediatric leukemia.
Fusion oncoproteins are created when two genes are joined abnormally. NUP98 fusion oncoproteins are known to drive aggressive childhood leukemias. But researchers did not understand how the process worked.
“We’ve demonstrated that the NUP98 family of fusion oncoproteins help transform blood stem cells by driving phase separation and thereby driving an expression program that leads to leukemia,” said co-corresponding author Richard Kriwacki, PhD, Structural Biology.
Findings have now revealed the types of interactions that underlie how NUP98 fusion oncoproteins phase separate. The findings apply to four types of NUP98 fusion oncoproteins that help transform blood stem cells leading to leukemia. Research also suggests the findings are applicable to other fusion oncoproteins beyond NUP98.
“By providing proof-of-principle evidence showing that phase separation is key to transforming blood stem cells, we’ve set the stage for future studies into how to alter phase separation therapeutically,” said co-corresponding author Charles Mullighan, MBBS, MD, Pathology.
Cancer Discovery published this work.