Clinical Review Science, medicine, and the future

Childhood leukaemia

BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7332.283 (Published 02 February 2002) Cite this as: BMJ 2002;324:283
  1. Mel Greaves, professor of cell biology (m.greaves@icr.ac.uk)
  1. Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB

    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

    Methods

    This article is based on information and views published from my laboratory plus comprehensive, prospective screening of leading journals for leukaemia and cancer research.

    A diverse disease with variable clinical outcome

    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 …

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