Leukaemia: how can stem cells help? | Eurostemcell

Like most cancers, leukaemias are caused by a series of rare mutations (changes) in certain genes. These generally arise spontaneously at a very low rate inside primitive blood cell precursors throughout life. Very rarely, a mutated form of one of these genes may be inherited. When this happens the individual is highly predisposed to develop leukaemia. Other known, but also rare causes include accidental exposure to radiation or prior treatment with some types of anti-cancer drugs. However, in order for a full blown leukaemia to develop, it is thought that several changes usually have to be accumulated in order to permanently alter the programs that control normal blood cell production.

A large number of gene mutations have been linked to causation of human leukaemias, and in some cases, the same mutation is consistently and uniquely associated with a particular type of leukaemia. Chronic myeloid leukaemia (CML) is an example of a leukaemia where knowledge of a shared mutation led to the development of a drug (Gleevec) that is very successful in killing the leukemic cells in patients that are diagnosed with early stage (chronic phase) CML. However, in most patients with other types of leukaemia, the diversity of mutations that are present in their cells has made the development of effective targeted therapies more challenging.

Because many types of leukaemia are thought to require several rare mutations in order to develop, the first change is assumed to occur in a cell that will remain in the body for a long time. A prime candidate group of cells are the most primitive blood cell precursors - also called haematopoietic stem cells (HSCs).HSCs are responsible for making new blood cells in our bodies for our entire lives. If a stem cell is affected by a genetic change, all the cells it produces will inherit the same mutation. It has been shown that CML starts with a particular mutation in an HSC. However, the daughters of that first cell to be mutated then go through a number of steps to develop into mature white blood cells. The acquisition of new mutations can happen at any of these steps.

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Leukaemia: how can stem cells help? | Eurostemcell