Lightening the leukaemia load for kids with Down syndrome

Dr Rishi Kotecha, Dr Laurence Cheung and Dr Sébastien Malinge

Kids born with Down syndrome are at high risk of an array of health problems – including issues with sight, hearing, heart defects, bone complications, immune disorders and learning difficulties. One of the lesser-known complications is their increased risk of childhood leukaemia.

Acute leukaemia is the most common type of cancer in children, affecting more than 200 Australian children annually. But some children are more prone than most, with those born with the genetic disorder Down syndrome carrying a 27-fold risk of developing B-cell leukaemia.

Not only are kids with Down syndrome at higher risk of developing leukaemia, but they also have a harder time fighting it – responding poorly to current treatments and facing triple the risk of having toxic secondary effects. They are also at almost twice the risk of relapse compared to other children.

It’s a load The Kids cancer researcher, Dr Sébastien Malinge, has dedicated more than a decade of his career to lightening. 

“I’ve been fortunate enough to meet many children with Down syndrome over the last ten years, and their warmth and kind nature continues to inspire me,” Dr Malinge said.

“I felt genetics had been unfair to these kids. They’re at an increased risk of lymphoid leukaemia and are given a far worse prognosis – and that’s what drives me, finding the genetic causes of this to give them the same fighting chance against leukaemia as any other kid.

Dr Malinge began this work as a PhD student in Paris in 2006, using a sample donated by a Down syndrome child in France to try to better understand the relationship between Down syndrome and cancer. Focusing on chromosome 21 – an extra (third) copy of which leads to Down syndrome – Dr Malinge and colleagues were able to show the same chromosome is implicated in a range of blood cancers, in children with and without Down syndrome.

Dr Malinge subsequently used another half a dozen samples to develop the world’s first Down syndrome preclinical models. Since moving to The Kids Research Institute Australia in 2017, he has gone one better – developing the world’s first Down syndrome cell line. Using the models and this cell line, he is now working to identify new weaknesses in leukaemia cells and testing novel therapies to help improve treatments and outcomes.

“There are many lessons to be learnt from studying leukaemia in children with Down syndrome,” Dr Malinge said. “Extra copies of chromosome 21 are one of the most common genetic features in kids with blood cancer, and we have recently established that they also have a role outside Down syndrome patients.

“This knowledge is giving us new clues about the mechanism behind other types of leukaemia in kids – possibly even lymphoma in adults.”

Dr Malinge and his team are currently using the unique lab models they built to screen a wide range of drugs and therapies.

“We have already tested some drugs to decrease the growth of leukaemia cells and we are looking at widening this scope to other types of drugs,” Dr Malinge said.

“Through this process, we are finding new vulnerabilities to attack the cancer – not only paving the way for more efficient, more targeted therapies for kids with Down syndrome – but also non-Down syndrome children with leukaemia and lymphoma. That’s the ultimate goal.”