Study of the side-effects of the anti-leukaemia drug Asparaginase

26 June 2014
Dr Oleg Gerasimenko, Cardiff University

Asparaginase is an important drug used in the treatment of childhood leukaemia. However, in some children it causes pancreatitis, a life-threatening inflammation of the pancreas.

In this project, the team will examine the mechanisms underlying the development of pancreatitis and test new ways of reducing the side-effects of Asparaginase treatments.

Amount of grant: £248,436 | Date of award: June 2014


Asparaginase is an anti-leukaemic drug, forming an important part of the chemotherapy regime of most young leukaemia patients.  

Asparaginase can, however, cause a life-threatening inflammation of the pancreas – known as pancreatitis. Once children develop pancreatitis they cannot receive any more Asparaginase, compromising their chance of beating leukaemia.

Dr Gerasimenko and colleagues in Cardiff are examining the mechanisms by which Asparaginase causes pancreatitis, with the ultimate aim of being able to protect pancreatic cells.

They know from previous work that one of the features of the acute pancreatitis pathway is elevated calcium levels in cells. They have successfully demonstrated that reduction of calcium levels, either by inhibiting calcium release within cells or external calcium entry, dramatically improves survival of pancreatic cells treated with alcohol or bile. In preliminary experiments they have shown that these approaches can also protect pancreatic cells from side-effects of Asparaginase.

They are now carrying out further tests and developing prototypes of potential drugs to improve leukaemia treatments. This work may also enable identification of children who are likely to get pancreatitis before they are exposed to Asparaginase, so that they can be offered alternative treatments.

About the research team

Dr Oleg Gerasimenko is one of the UK’s leading experts on acute pancreatitis. Together with Dr Julia Gerasimenko, he has significantly advanced understanding of the mechanisms underlying development of this condition. Their lab is one of the leading laboratories in the calcium signalling field with a very strong international reputation.

To help translate their work to clinical practice, the team in Cardiff is collaborating with Dr Sujith Samarasinghe, Consultant Paediatric Haematologist at Great Ormond Street Hospital and one of the UK’s leading authorities on treatment toxicity.

What difference will this project make?

The team will test two very promising approaches for the treatment of acute pancreatitis. Each of these approaches has the potential to improve future treatments for children with leukaemia, to help avoid this life-threatening side-effect.

The team’s work may also enable the identification of children who are likely to get pancreatitis before they are exposed to Asparaginase, so that they can be offered alternative treatments.

"This is a very important project that will go a long way to achieving the objective of developing a cure for Asparaginase-induced Acute Pancreatitis."
External reviewer

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