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

许多癌症被认为是由一群罕见的干细胞维持的，这些干细胞能够逃避目前的治疗方法。这些癌症干细胞能够无限次分裂，并且能够发育成肿瘤内的每一种不同的细胞。这意味着，如果它们在最初的治疗中没有被完全清除，它们就会引发癌症的复发。与许多肿瘤不同，我们已经证明，在儿童急性淋巴细胞白血病中，处于不同发育阶段的癌细胞能够表现得像干细胞一样。这项研究的目的是研究允许这些白血病细胞引起复发的遗传程序。已知PIWIL2基因在睾丸干细胞中很重要，睾丸干细胞是精子的形成细胞。在包括儿童白血病在内的许多癌症中也发现了PIWIL2。通过阻止和迫使白血病细胞产生PIWIL2，我们可以评估该基因对这些细胞导致疾病复发的能力的影响。我们将研究与PIWIL2相关的遗传途径，以确定其他重要基因，这些基因可能在未来为开发新药提供靶点。

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.