Science, medicine, and the future: Childhood leukaemia

Abstract

Molecular genetics provide exciting new insights into the pathogenesis of childhood leukaemia The risk of any child developing acute leukaemia is about 1 in 2000 with 400-450 new cases a year in the United Kingdom. Cure rates approaching 75% can be achieved with combination chemotherapy, but this figure disguises success rates that vary from 10% to 90% with the different biological subtypes of the disease. In this review I discuss how new insights into the underlying molecular biology of leukaemia have changed our understanding of the disease. Not only is there the prospect of better treatment and the introduction of new biologically based therapies, but, as the causes of disease are being unravelled, the possibility of prevention may not just be wishful thinking. #### Summary points Different chromosomal and gene abnormalities in leukaemia define biological subsets of disease with prognostic importance Chromosome translocations generate chimeric fusion genes, which provide stable sensitive markers that are unique for each patient's leukaemic clone and can be used to track its origins and response to treatment The common chromosome translocations in childhood leukaemia seem to initiate disease and often arise prenatally One or more postnatal genetic alterations are also needed for leukaemia development, and in childhood acute lymphoblastic leukaemia these may be caused by abnormal immune responses to infection Proteins coded by fusion genes operate principally by blocking cell differentiation in leukaemic cells and provide potential targets for new treatments This article is based on information and views published from my laboratory plus comprehensive, prospective screening of leading journals for leukaemia and cancer research. It has long been recognised that childhood leukaemia is not one homogeneous disease. The major morphological division into acute lymphoblastic leukaemia and acute myeloblastic leukaemia is supplemented by the identification of a range of subsets based on gene expression, antigens that delineate cell …