Understanding GATA2: How one molecule may hold the key to treating lymphoedema

Natasha Harvey (right) with members of her CCB labResearchers at the Centre for Cancer Biology – an alliance between UniSA and SA Pathology – have unlocked another piece of the gene puzzle in relation to the debilitating condition of lymphoedema.

Affecting more than 140 million people worldwide, lymphoedema is an inherited condition but can also be caused by serious damage or injury to the lymphatic system. Modern treatments for cancer including the removal of lymph nodes or damage through radiation therapy can cause lymphoedema.

The debilitating symptoms include localised fluid retention and tissue swelling because the lymphatic system is too compromised to function normally.

In a study published today in the Journal of Clinical Investigation, UniSA’s Associate Professor Natasha Harvey and her team have been focussing on the role of GATA2, a molecule that binds to DNA to switch genes off or on, and one that is vital to building the vessels in the lymphatic system.

“Our initial work uncovered that mutations in the gene GATA2 are causative of Emberger Syndrome (ES), an illness in which patients have lymphoedema and a predisposition to developing myelodysplastic syndrome (MDS) and or acute myeloid leukaemia (AML),” Assoc Prof Harvey says.

“We could see that GATA2 had a very important role to play in lymphatic vessel development, so we wanted to explore that further.

“We have now identified that it is GATA2’s ability to bind to specific regions of DNA that ensures some genes are switched on or off in the important vessel valves of the lymphatic system.

“In some patients with lymphoedema GATA2 seems to have lost the ability to bind with the DNA to switch on the genes vital to valve development and function.

“The research posits a molecular explanation for the development of lymphoedema in patients with ES and it gives us clues as to why GATA2 is so important and what further research might deliver.

“Our ultimate goal is to really understand GATA2 – to know in complete detail the molecular mechanisms by which it controls lymphatic vessel valve development. That will be a vital step on the path to designing new therapeutic agents able to treat lymphoedema.”

Dr Harvey’s team collaborated closely with the CCB’s Professor Hamish Scott and team, as well as national and international laboratories, in the research. Read Dr Harvey’s research paper in JCI.

Media contact: Michèle Nardelli office: +61 8 8302 0966 mobile: 0418 823 673 email: michele.nardelli@unisa.edu.au or Kelly Stone office: +61 8 8302 0963 mobile: 0417 861 832 email: kelly.stone@unisa.edu.au

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