In vivo modulation of the stem cell programme of cancer stem cells in childhood acute lymphoblastic leukaemia

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A number of cancers are thought to be maintained by a rare population of stem cells which are able to evade current therapies. These cancer stem cells are able to divide an infinite number of times, as well as being able to develop into each of the different cells within a tumour. This means that if they are not completely removed by initial treatment, they are able to initiate relapse of the cancer. Unlike many tumours, we have shown that in childhood acute lymphoblastic leukaemia, cancer cells at different stages of development are able to behave as stem cells. The aim of this fellowship is to investigate the genetic programme which allows these leukaemic cells to cause relapse.The gene PIWIL2 is known to be important in testicular stem cells, which form sperm. PIWIL2 has also been found in a number of cancers, including childhood leukaemia. By both preventing and forcing leukaemic cells to make PIWIL2, we can assess the effects of this gene on those cells‘ ability to cause disease relapse. We will look at the genetic pathways associated with PIWIL2 to identify additional important genes which may, in future, provide targets against which new drugs can be developed.