Cell darwinism, apoptosis, free radicals and haematological malignancies

Abstract 

Haematopoiesis can be interpreted as an ecosystem composed of billions of cells interacting according to Darwinian rules. Mutation, by promoting cell diversity, ensures versatility in coping with internal and external challenges. Most mutated cells are eliminated through apoptosis. However, if mutation generates relative resistance to apoptosis it may result in growth advantage for the mutated cells. The probability of monoclonality and malignancy is significantly increased if the normal multiclonal environment is damaged by a pathologic proapoptotic process that spares the apoptosis resistant clones. Paroxysmal nocturnal haemoglobinuria, myelodysplastic syndromes, chronic myeloid leukaemia, secondary acute leukaemias and immunosuppression-related non-Hodgkin’s lymphomas can be interpreted as ‘opportunistic’ clonal and malignant diseases. Free radicals (FRs) are closely linked to apoptosis and have been incriminated in oncogenesis. Conditions associated with increased FR formation or impaired FR disposal may provide the enhanced apoptotic background against which an apoptosis-resistant clone may gain growth advantage.

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