Pinpointing people who are at risk of relapsing
In a third of acute myeloid leukaemia (AML) patients, the leukaemia cells have a faulty copy (mutation) of the nucleophosmin (NPM1) gene. Some patients can be cured with just chemotherapy, while approximately half suffer a relapse, many of whom will die. We wish to understand the reasons for the marked variation in treatment response. It is now clear that AML is complex, with each leukaemia composed of different populations of cells that can vary in their genetic make-up, potentially affecting their sensitivity to treatment. It is possible that more primitive cells might be able to lie dormant and resist chemotherapy, causing subsequent relapse. We have been using sensitive tests to detect cells with the NPM1 mutation in the bone marrow, showing that patients, in whom these are slow to clear or persist following therapy, are at a very high risk of disease recurrence. We plan to look at this small reservoir of cells in detail to understand which sub-populations they come from. In the future the results of this research could allow us to better advise AML patients about their risk of relapse and treatment options, provide targets for new therapies and give a better chance of long-term survival.