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Research Focus: Investigating the genetic pathways that control leukaemia growth

A study in 2017 suggested that cells reduce the amount of the gene USP9X in their cells

Project title: RNA helicase DDX3X regulates JAK-STAT signalling in acute lymphoblastic leukaemia

Lead investigator: Dr Lisa Russell, Newcastle University
Funded by The Little Princess Trust in partnership with CCLG
Awarded January 2019

Award: £100,580

There are patients with leukaemia that have errors in their genetic code which leads to a set of genes (gene pathway) being switched on and allows cells to grow quickly. If this gene pathway is switched on too much, it can actually cause the cells to die. Therefore, cells becoming cancer cells need to balance the level of this gene pathway to ensure they can grow much quicker than healthy cells.

A study in 2017 suggested that cells reduce the amount of the gene USP9X in their cells, so the gene pathway can be slowed down. We want to understand what role the gene DDX3X has in slowing this gene pathway. We deleted DDX3X from the genome of leukaemic cells and found they were unable to grow. We also noticed a relationship between the levels of USP9X and DDX3X.

We have five aims:

To identify all the genes that are controlled by DDX3X in leukaemia cells.
Identify where in the cell DDX3X is located.
To investigate the effect of switching off other interacting gene pathways.
Create the joining of USP9X to DDX3X to prove it will reduce the gene pathway. 
Treat patient cells with a drug to block DDX3X and monitor the effects on their growth and survival.

By understanding more about what controls this important pathway in leukaemia cells, we will be able to develop therapies that will specifically benefit those with activation of this pathway.

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