Nav: Home

New study discovers genetic changes linked to leukaemia in children with down's syndrome

July 11, 2019

Researchers at the University of Oxford, in collaboration with colleagues from Hannover Medical School and Martin-Luther-University Halle-Wittenberg, have discovered the specific gene mutations that are required for the development of leukaemia in children with Down's syndrome. Children with Down's syndrome have a 150-fold increased risk of myeloid leukaemia, and while some of the genetic causes of this have been previously established, this is the first study to identify a wide range of mutations and how they functionally interact to lead to leukaemia. The study was published today in the journal Cancer Cell.

'We already knew that 30% of babies born with Down's syndrome have acquired a change in a gene called GATA1 in their blood cells. This is not an inherited genetic change, but one that occurs and will remain only in the baby's blood cells," says study author Professor Paresh Vyas, from the MRC Weatherall Institute of Molecular Medicine at the Radcliffe Department of Medicine, University of Oxford. "The abnormality in the GATA1 gene can be detected by a simple blood test at birth. Babies with an altered GATA1 gene have a predisposition to develop leukaemia, and we often refer to this as 'myeloid preleukaemia'.'

Of the 30% of children with Down's syndrome who are found to have 'myeloid preleukaemia', only 10% of those will go on to develop myeloid leukaemia (3% of all children with Down's syndrome). Until now, it was not understood why only some children with the GATA1 mutation were progressing to full leukaemia, while others were not.

'90% of babies with Down's syndrome do not go on to develop preleukaemia. But until now, we did not fully understand why some babies did develop leukaemia,' says Vyas, who is also a group leader at the MRC Molecular Haematology Unit. 'To answer this question, we carefully characterised the mutations in genes required for leukaemia to develop. We found that additional genetic changes are required in the altered GATA1 blood cells, and these additional changes transform the preleukaemic blood cells into leukaemic blood cells.' In total, 43 different altered genes were found.

The discovery of which specific genetic changes are required for leukaemia to develop has practical implications. While children with Down's syndrome are currently tested at birth for the GATA1 mutation, it may now become possible in the future to test for the additional mutations too. 'This would mean that we could identify the 10% of children who will develop leukaemia more quickly and easily, and importantly reassure 90% of families whose children will not develop leukaemia,' says Vyas. 'The identification of these genetic changes may also mean we can develop and test new treatments specifically targeting the genetic changes we now know are required by the leukaemia - and so develop more targeted treatments with less side effects.'

Current treatments for Down's syndrome children with leukaemia are already highly successful, and off the back of this research, another possible drug treatment has come to light. The drug Ruxolitinib, which is currently used to treat some blood conditions, could potentially be used to treat some of the specific genetic mutations found in the study. Clinical trials of the drug are a possibility for the future.

'The recent identification of a group of genes linked to leukaemia in children with Down's syndrome is an important first step towards developing early diagnostic tests and identifying effective treatments to help these patients,' says Dr Mariana Delfino-Machin, Programme Manager at the Medical Research Council (MRC). 'The MRC is proud to support the research undertaken at the MRC Molecular Haematology Unit, of which this early-stage study is a great example.'
-end-


University of Oxford

Related Leukaemia Articles:

Leukaemia cells can transform into non-cancerous cells through epigenetic changes
Researchers of the Josep Carreras Leukaemia Research Institute discover that a leukaemic cell is capable of transforming into a non-cancerous cell through epigenetic changes.
Published a clinical guide for the genomic diagnosis of Myelodysplastic Syndromes and Chronic Myelomonocytic leukaemia
A collective work between researchers from 8 research centres and hospitals in Spain, coordinated by Francesc Solé of the Josep Carreras Leukaemia Research Institute (IJC), and Esperanza Such, of the University and Polytechnic Hospital de la Fe describes the recommendations of use of the Next Generation genome Sequencing (NGS) in the diagnosis of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML).
Old cells, new tricks -- important clue to AML diagnosis and cure discovered
Around 22,000 people will be diagnosed this year in the US with acute myeloid leukemia (AML), the second most common type of leukemia diagnosed in adults and children.
New drug providing hope for babies with aggressive Acute Lymphoblastic Leukaemia
A breakthrough new drug is providing hope to tiny babies at risk of dying from an aggressive form of Acute Lymphoblastic Leukaemia and could help all cancer patients.
New study discovers genetic changes linked to leukaemia in children with down's syndrome
Researchers at the University of Oxford, in collaboration with colleagues from Hannover Medical School and Martin-Luther-University Halle-Wittenberg, have discovered the specific gene mutations that are required for the development of leukaemia in children with Down's syndrome.
First major study of proteins in patients with acute lymphoblastic leukaemia
The most common form of childhood cancer is acute lymphoblastic leukaemia (ALL).
Cancer causes premature ageing
New research shows that cancer causes premature ageing. Researchers studied Leukaemia, and found that it promotes premature ageing in healthy bone marrow cells.
Research reveals mechanism for leukaemia cell growth, prompting new treatment hopes
A mechanism which drives leukaemia cell growth has been discovered by researchers at the University of Sussex, who believe their findings could help to inform new strategies when it comes to treating the cancer.
From eye drops to potential leukaemia treatment
An active ingredient in eye drops that were being developed for the treatment of a form of eye disease has shown promise for treating an aggressive form of blood cancer.
Breast cancer drug could be used to treat life-threatening leukaemia
A recently-approved breast cancer drug could be used to target and treat a life-threatening leukaemia, new research has revealed.
More Leukaemia News and Leukaemia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab