NUI Galway researchers identify enzyme which plays key role in spread of blood cancer cells

Professor of Haematology at NUI Galway, Michael O’ Dwyer.

Professor of Haematology at NUI Galway, Michael O’ Dwyer.

Groundbreaking research being carried out at NUI Galway could lead to new ways of overcoming resistance to treatment for the blood cancer multiple myeloma.

Researchers at the university have identified an enzyme that plays a key role in the spread and survival of blood cancer cells.

The discovery, which focused on multiple myeloma, was published recently by the internationally acclaimed journal, Blood.

The condition results from an overproduction of plasma cells, the white blood cells which produce antibodies. It leads to problems such as anaemia, bone damage, kidney failure and elevated calcium levels. There are about 240 new cases of multiple myeloma diagnosed each year in Ireland.

The research team was led by Health Research Board (HRB ) clinician scientist, Professor Michael O’Dwyer and Professor Lokesh Joshi of the university’s Glycoscience Group, which is supported by Science Foundation Ireland.

The group studies the complex sugars which cover all cells in the human body and many of the proteins in the bloodstream. Dr Siobhan Glavey, a medical doctor funded by the HRB, also had a key role lead in the study and was lead author on the paper.

Professor of Haematology at NUI Galway, Michael O’ Dwyer, says while treatments for multiple myeloma have improved over the last decade, and most patients are living longer, there is no cure.

“Our research is crucial because it sheds new light on the biology of multiple myeloma which could lead to new strategies to overcome resistance to treatment.

“Working in close cooperation with Dr Irene Ghobrial from the Dana Farber Cancer Institute at Harvard in the US and colleagues from the Institute of Cancer Research in the UK, we focused on alterations in a process called glycosylation, a process whereby proteins and lipids are modified by specific sugars, because of its role in cell-cell interactions and the spread of cancer cells in the blood.”

In essence we have linked the overproduction of a specific enzyme called sialyltransferase to disease progression and worse outcomes in multiple myeloma, he explains.

“The increase in this enzyme activity causes a series of knock-on effects; increasing glycosylation, which in turn increases the interaction of the cancer cells with receptors on the walls of blood vessels called selectins which then encourages their circulation, spread and retention in the bone marrow.

“Our aim now is to prevent these interactions that cause the spread using specific enzyme and selectin inhibitors.”

Dr Graham Love, CEO of the HRB, commented on the importance of the research: “Understanding what causes multiple myeloma to progress, or generate worse outcomes, is the first step towards improving treatment. This discovery reinforces the transformational role our clinician scientists have in bringing real clinical questions to a research environment and delivering results back to the bedside.”

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