The biology of normal and leukaemic stem and progenitor cells

01 September 2010
Professor Tariq Enver, UCL Cancer Institute

Leukaemia arises because of accumulated genetic mutations arising in blood stem cells. Some early mutations occur before birth and Professor Enver has shown that children carrying these early mutations harbour a pre-leukaemic stem cell. By itself, this cell is harmless, disappearing with age, but if it acquires additional mutations, it can trigger full-blown leukaemia. The team now seeks to understand why these pre-leukaemic cells cause leukaemia in some children but not others.

Amount of grant: £330,000  |  Date of award: September 2010

Stem cells and blood production

Our bone marrow produces millions of blood cells every day.

Three types of cell are produced – red blood cells, white blood cells and platelets.Three types of cell are produced – red blood cells, white blood cells and platelets. Red blood cells carry oxygen around the body, white blood cells fight infection and platelets help our blood to clot following injury.

These blood cells originate from rare stem cells within our bone marrow.

Stem cells have the unique ability to simultaneously renew themselves (to maintain the pool of stem cells) and to generate progenitor cells, which can in turn develop into mature blood cells when required by the body.

When things go wrong

Leukaemia arises because of accumulated genetic mistakes (mutations) arising in single stem cells.

It is known that some early or ‘initiating’ mutations occur before birth but only one per cent of children born with such mutations will actually develop leukaemia.

Identical twins give crucial insight

Working with pairs of identical twins in which one twin has developed leukaemia, Professor Enver has revealed that children carrying initiating mutations harbour a pre-leukaemic stem cell.

By itself, this cell is harmless and disappears with age. However if it acquires additional mutations, it can develop into a leukaemic stem cell, triggering full-blown leukaemia.

Twins with leukaemia: Ethan and Kai Thompson | Tomas and Daniel Cowpe

World-leading research into leukaemic stem cells

Research is now underway to understand why pre-leukaemic stem cells are converted to leukaemic stem cells in some children but not others.

Professor Enver’s team is aiming to map out the molecular mechanisms that control the function of normal stem cells. They want to understand how these mechanisms go wrong, leading to the production of vast numbers of abnormal white blood cells (leukaemia).

How this research will benefit children with leukaemia

Professor Enver is working with the team at Great Ormond Street Hospital to look at the persistence of the leukaemic stem cell during treatment.

They want to establish whether regular chemotherapy eliminates leukaemic stem cells, the root cause of the disease, rather than just the abnormal blood cells that form the bulk of the leukaemia.

The persistence of leukaemic stem cells could explain why some children relapse after conventional chemotherapy. If this is established, new treatments can be designed that specifically target leukaemic stem cells.

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