Posted on 8th August 2019 by Bethan Warman

Understanding the genetics of familial leukaemia

In the majority of patients, cancer is caused by the accumulation of changes to the genetic code that are acquired overtime during a person’s life. These can be in response to environmental factors, such as tobacco and ultraviolet radiation, or can occur as the individual ages. However, genetic faults can also be passed on from a parent to a child if mutations occur within sperm or egg cells and, as a result, the child inherits a predisposition to developing cancer, typically with high penetrance and earlier onset of disease, compared with sporadic forms of these diseases.

An example of a group of cancers which can have an inherited component are myelodysplastic syndromes (MDS). MDS are malignant blood disorders which cause a reduction in the number of normal blood cells and are associated with an increased risk of the development of acute myeloid leukaemia (AML). Although considered rare, the true frequency of inherited/familial MDS and AML remains unknown.

Over the last two decades, multiple gene alterations have been identified that are responsible for an inherited/familial predisposition to MDS/AML. In 2014, the charity Bloodwise awarded a 5-year programme grant to a team from Queen Mary University of London to support research to better understand the nature of these faulty genes.

Important information for the patients and their families

The team of researchers from the Barts Cancer Institute, led by Professor Jude Fitzgibbon, and the Blizard Institute, led by Professors Tom Vulliamy and Inderjeet Dokal, have collected, stored and analysed blood and bone marrow samples from over 100 families with inherited MDS/AML. The Bloodwise research funding allowed the group to set up genetic testing for patients who present with suspected familial MDS/AML in the clinic and where a germline predisposition is confirmed, this allows for the provision of appropriate management and counselling for the patient and their family.

Recognition of inherited MDS/AML predisposition can also impact the therapy a patient receives. Depending on the mutations present, treatments can be tailored specifically for a patient’s disease in order to achieve optimal outcomes. In addition, when selecting bone marrow/stem cell donors, the haematologist needs to be vigilant and ensure that an asymptomatic family member with the same genetic defect is not used as a donor, as several examples in the literature have shown a recipient to go on to develop MDS/AML again in the future.

Not only does this research provide valuable information for the families affected in terms of management and treatment, but it is also opening the door for new biology with the identification of novel genes implicated in familial AML/MDS that are not recognised in sporadic disease. In addition, if a patient does not have a genetic defect in one of the known familial MDS/AML loci, but there is a strong suspicion for an inherited disorder due to the presence of MDS/AML in multiple family members, then samples from these patients may be used in basic research studies aimed at identifying other gene alterations which may be linked to inherited MDS/AML. This is the major focus of the group’s research today.


Further information:

Watch Professor Fitzgibbon’s interview with the MDS UK Patient Support Group at the UK MDS Education Forum.


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