Cell darwinism, apoptosis, free radicals and haematological malignancies

Haematopoiesis can be interpreted as an ecosystem composed of billions of c ells interacting according to Darwinian rules. Mutation, by promoting cell diversity, ensures versatility in coping with internal and external challen ges. Most mutated cells are eliminated through apoptosis. However, if mutat ion generates relative resistance to apoptosis it may result in growth adva ntage for the mutated cells. The probability of monoclonality and malignanc y is significantly increased if the normal multiclonal environment is damag ed by a pathologic proapoptotic process that spares the apoptosis resistant clones. Paroxysmal nocturnal haemoglobinuria, myelodysplastic syndromes, c hronic myeloid leukaemia, secondary acute leukaemias and immunosuppression- related non-Hodgkin's lymphomas can be interpreted as 'opportunistic' clona l and malignant diseases. Free radicals (FRs) are closely linked to apoptos is and have been incriminated in oncogenesis. Conditions associated with in creased FR formation or impaired FR disposal may provide the enhanced apopt otic background against which an apoptosis-resistant clone may gain growth advantage. (C) 2001 Harcourt Publishers Ltd.