Scientists at the Cancer Research UK Manchester Institute have gained new insight into a possible treatment target for leukaemia by looking at what makes blood stem cells stop replicating.

Replication of stem cells is a key process in maintaining normal tissue structure and function. Stem cells divide rapidly and there are certain defence mechanisms in place in case there are mistakes in these new cells – to hopefully stop the uncontrolled growth at the heart of cancer development.

In normal cells, one way of controlling replication is through senescence when the cell enters a resting phase and no longer divides. In contrast, in a type of blood cancer known as acute myeloid leukaemia, there is abnormal growth and proliferation of white blood cells – these collect in the bone marrow and prevent the production of normal blood cells.

Scientists have previously seen that in animals without a protein known as MOZ, which regulates the creation of blood stem cells, there is increased cell senescence.

Now our researchers from the Stem Cell Biology group have investigated how the activity of MOZ is linked to both proliferation and senescence in stem cells.

Dr Georges Lacaud, who led the research, said: “The uncontrolled growth and proliferation of cancer cells driven by abnormal replication is a hallmark of cancer – understanding this process will help us to identify new strategies for developing anticancer treatments. Currently, little is known about the control of senescence–our aim was to explore and better understand the part played by MOZ”

The Stem Cell Biology group describe their findings in a recent paper in the journal Stem Cells. They show that a lack of MOZ leads to an increase in expression of the p16 gene, which plays a key role in suppressing tumours. This increase in p16 led to more cells entering senescence. In both blood and neural stem cells, MOZ appears to help maintain the ability to replicate.

Dr Lacaud added: “It seems that MOZ is responsible for blocking expression of p16 – this may well be an important stage in the development of leukaemia. Future treatments could target MOZ to prevent it from blocking the tumour suppressor activity of p16 and may provide a novel strategy to stop cancer stem cells dividing.”