Shwachman-Diamond-Syndrome (SDS) is an inherited disease that affects 1 in every 76,000 children. Dysfunction of the child’s blood and circulatory system occurs in nearly all patients, causing increased rates of infection and decreased capacity to transport oxygen. Unfortunately, the overall survival of a young person with SDS is only 35 years, and this is attributed to sepsis, organ failure and most frequently the development of leukaemia. 

At the current time, detailed knowledge about disease progression from SDS to leukaemia is significantly lacking, with no mechanistic understanding of transformation. Detailed analysis of SDS patient samples is desperately needed if we are to increase the survival and quality of life of patients. Importantly, the sophisticated technologies and expertise needed for a detailed characterisation of the disease is only available to a few laboratories and individuals from around the world, and therefore the missing pieces of the SDS puzzle have remained a mystery. 

Over the last 3 years thanks to the support of HMRI and in particular the Hunter District Hunters Club, the Estate of James Scott Lawrie and the Ski Club for Kids we have studied the function of the gene that is at the heart of this syndrome, the SBDS gene, in leukaemia cells. This research was initiated following the discovery that the SBDS protein is an inhibitor of the tumour suppressor protein, PP2A, in acute myeloid leukaemia (AML), the deadliest form of leukaemia (the results of this work are currently under review for publication). Although the AML cells used in this initial study expressed a wildtype SBDS protein, the results suggested a mechanism for PP2A inhibition that may be associated with leukaemogenesis, and that may explain why SDS patients develop AML.

This project brings together basic scientists with paediatricians and haematologists from the John Hunter Children’s Hospital, the Calvary Mater, Newcastle and the Lady Cilento Children’s Hospital, Brisbane to determine whether bone marrow cells from local and interstate SDS patients (ages 5-21) have similar characteristics to what we have shown in our previous study investigating AML. If the findings from this project confirms our hypothesis, we have already developed drugs that target the aberrant SBDS protein, and thus are likely to be effective in treating SDS. If the findings do not support our hypothesis, novel detailed information about the SDS disease will be discovered and we will focus on developing alternative treatment strategies. 

Our group is the only research group dedicated to the study of SDS in Australia. SDS is a devastating disease that currently lacks a definitive cure, with inefficient treatment strategies available to patients. As SDS is a rare disease research into disease progression is desperately lacking. This project will bring together clinical and biomedical experts to provide more details about how mutations to the SBDS gene lead to SDS and subsequently promote the development of leukaemia.


Dr Matt Dun, Dr Nikki Verrills, Dr Jeremy Robertson

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