What links Down Syndrome and childhood leukaemia?

In short: we don’t know – but scientists at the WIMM are hoping to find out. Just over a year ago, Professor Irene Roberts moved from the Hammersmith Hospital in London to the WIMM, where she is continuing her long-standing research into haematological disorders that affect newborn babies – particularly those with Down syndrome. In this blog, Dr. Barbara Xella talks to Irene about her work, and how she hopes it will help to improve diagnosis and treatment of these devastating childhood disorders.

A few days ago I sat down for a chat with Professor Irene Roberts, a group leader at the Molecular Haematology Unit here in the WIMM (and a Consultant and Professor of Paediatric Haematology) to find out more about the research carried out in her lab.

I was fascinated by the story of how her research developed over the course of two decades. More than 20 years ago, when Irene was working as a Paediatric Haematologist in London, she routinely analysed hundreds of blood samples coming from newborn babies.

She soon realized that she could immediately tell whether a baby was born with Down syndrome – or trisomy 21, which means that three copies of chromosome 21 were present in the cells of the body instead of two – just by having a quick look at the baby’s blood.

Our blood consists of several different types of specialized cells – red blood cells, white blood cells and platelets – that all have to be produced and maintained in specific proportions. This critical balance is dramatically disturbed in babies with Down syndrome.

Strikingly, Irene found that there was a strong bias towards production of cells belonging to the red cell lineage, accompanied by a dramatic impairment in the development of some types of white blood cells and platelets.

Because she was seeing this phenomenom over and over again in the blood of newborn babies with Down syndrome, she became convinced that something about the presence of that extra copy of chromosome 21 was perturbing blood cell production from very early on in development of the embryo.

Unfortunately, because of this profoundly altered equilibrium between blood cell production during foetal life, newborn babies with DS are prone to develop a unique, transient form of leukaemia called TAM (Transient Abnormal Myelopoiesis). Not only that, but sadly young children with Down syndrome are also vulnerable to developing a full-blown acute leukaemia termed Myeloid Leukaemia of Down syndrome (ML-DS) during the first few years of their lives.

Irene’s work focuses on understanding what is about that extra copy of chromosome 21 that interferes with the genes and proteins that control blood production early in life.

A key idea that drives Irene’s research is that red blood cell production is the default when blood cells are first produced during development in the womb, as foetuses need their own blood system (independent from their mother’s) right from the very beginning, whereas, it is only later in foetal life when a switch occurs that accelerates the production of white blood cells that make up our immune system.

This is probably because during embryonic development a baby is protected from infection by its mother and therefore has no need for an immune system of its own until it is born.

Irene thinks that molecular signals coming from the extra chromosome are preventing this switch from occuring properly, thus impairing white blood cell development and creating the bias towards red blood cell production.

Working together with Professor Paresh Vyas, who also has a lab in the WIMM, Irene is trying to discover the molecular mechanisms involved in this outcome by combining studies both in the lab and in the clinic. She hopes that their findings will help identify children with Down syndrome who are at risk of developing leukaemia, and design treatment strategies to reduce this risk.

Importantly, this work will not only lead us to understand the causes of leukaemogenesis in Down syndrome, but also help us unlock the mechanisms of childhood leukaemia in general.

Post written by Barbara Xella, and edited by Irene Roberts and Bryony Graham.