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Category:Domain namesHuman leukocyte antigens and leukaemia: what can we learn from a genetic perspective?
This review describes approaches to the study of gene expression in leukaemia and describes some of the genetic changes occurring in the disease. Two aspects of this field are addressed: alterations in genes associated with a predisposition to the disease and the expression of genes involved in normal growth control. The finding that the most common genetic change in leukaemia is a translocation between the immunoglobulin heavy chain and myeloma oncogene suggests that these two genes, when juxtaposed, may be directly responsible for malignancy. This has yet to be confirmed. Another common genetic event in acute leukaemia is that chromosome 8q24 is gained as a result of a gene on this chromosome being expressed. The fact that the p53 tumour suppressor gene is located on chromosome 17p and is mutated in up to half of all haematological malignancies may be relevant to our understanding of the pathogenesis of these diseases. Analysis of gene expression in acute leukaemia using an expression microarray approach has led to the identification of a number of genes with abnormal expression in the disease that may be important in leukaemia cell growth and differentiation. A ‘first pass’ search in the literature was performed to identify all genes reported to be altered in leukaemia cell lines or primary cells. A core list of 19 genes was extracted from this review and an additional 16 genes identified from the literature searches were included. This set of genes was used as a basis to determine whether they could be clustered into groups based on their pathway involvement in leukaemia. Our analysis of the data yielded three main categories: 1. genes with altered expression in common between cell lines and leukaemic cells but also present in normal tissues; 2. genes with altered expression in leukaemia cell lines but absent in normal tissues; and 3. genes with altered expression in leukaemic cells and absent in cell lines. Overall, this is an under-investigated field at present. With regard to the first group of genes, as the alteration in cell lines is often accompanied by leukaemia, some evidence for a link with malignancy is expected. With the second category, genes such as topois
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