University of Oxford researchers have identified a genetic “signature” for particularly aggressive variations of a range of common blood disorders.
The researchers, who were funded by the blood cancer charity Leukaemia & Lymphoma Research, hope that a routine test could soon help guide treatment for individual patients with disorders known as myelodysplastic syndromes (MDS).
In patients with MDS, normal blood production breaks down, with healthy cells underproduced and the bone marrow crowded with defective cells. MDS develops differently in patients but in up to 40% of cases, it can progress into leukaemia.
MDS is diagnosed in around 2,000 people in the UK every year and can be treated in a many ways - from palliative care to bone marrow transplantation. It is vital to establish the prognosis of each patient to consider appropriate treatment.
Prof Jacqueline Boultwood’s team at the University of Oxford used a technique called ‘gene expression profiling’, which scans the activity levels of thousands of genes simultaneously, on malignant stem cells from 125 MDS patients. The results are published online in the Journal of Clinical Oncology.
Following the patients’ progress for an average of four years, the study found a significant link between the activity of a set of 20 genes and long-term survival. The relationship between fatality and two genes was particularly strong, with the ‘WT1’ gene consistently overactive and ‘LEF1’ underactive in MDS patients with poor survival times.
The researcher’s genetic test outperformed other methods used currently by doctors. After three years around 70% of patients identified by the test at diagnosis as having a good prognosis were alive, compared to 30% of the poor prognosis group.
Professor Boultwood said: “Profiling of these genetic markers will help to deliver a more accurate and consistent prognosis for MDS patients. Identifying those at risk enables doctors to give early intensive treatment to those who need it most.”
Importantly, the test worked effectively on routine bone marrow samples taken from MDS patients, removing the need to purify leukaemic stem cells.
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “Mutations in MDS cells cause them to overproduce or underproduce key proteins, which then have a profound effect on patient survival. This research represents a significant step towards tailoring treatment for individual MDS patients.”