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Leukaemia lead from Down's gene

作者:姚嗜唁    发布时间:2019-02-28 09:16:04    

By Tim Thwaites THE EFFECTS of Down’s syndrome have pointed geneticists towards a gene which, when overactive, seems to cause cancer. The discovery may eventually lead to earlier diagnosis of acute myeloid leukaemia and better therapy for the disease, which affects about 1 in 6000 children and large numbers of adults. The research group at Monash University in Melbourne which has homed in on the gene is one of several studying people with Down’s as a way of finding out more about diseases that affect the general population. People with Down’s carry an extra copy of chromosome 21, and so produce up to one and half times the usual amounts of the proteins encoded by chromosome 21 genes. This causes cataracts, misshapen bones, frequent heart defects and learning difficulties. Down’s also leads to Alzheimer’s disease. “Many of these abnormalities reflect problems which occur in the general population as well,” says Ismail Kola, who led the Monash team. Down’s syndrome children are up to 70 times as likely as normal to contract acute myeloid leukaemia. Kola’s group suspected that the culprit is a gene on chromosome 21 called Erg, which belongs to a family of genes that code for transcription factors, which determine whether or not other genes are “read”. In 1993, a Japanese team discovered a genetic abnormality in which a copy of Erg is fused with a gene on chromosome 16. This was correlated with cases of acute myeloid leukaemia, suggesting that an overdose of Erg-encoded transcription factos is the source of the high leukaemia rates in Down’s patients. Kola and his team have now confirmed that an overdose of Erg can cause cancer. They inserted an extra copy of Erg into cultured mouse fibroblast cells, which are found in connective tissues. These cells normally clump together, but the addition of an extra Erg gene transformed them so that they divided and moved independently. When these cells were injected into mice, they induced tumours (Oncogene, vol 10, p 1423). The next step is to confirm the link with leukaemia. To do this, Kola’s team is creating transgenic mice which carry an extra copy of Erg in all their cells, to see whether these animals develop the disease. If acute myeloid leukaemia is caused by an overdose of the protein encoded by Erg, says Kola,

 

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