Evidence for a continuous decline in haemopoietic cell function from birth: application to evaluating bone marrow failure in children

There are considerable differences in haemopoietic activity between young c hildren and adults on the one hand, and between adults and the elderly on t he other. A fundamental unanswered question is whether these differences re late to discrete stages or are part of a continuous process. We have sought to define aspects of the haematological ageing process, and have found tha t results from children with bone marrow failure syndromes differ from age- matched reference values, Haemopoietic cells were obtained from umbilical c ord blood, from blood and bone marrow of healthy individuals and from the b lood of young patients with bone marrow Failure syndromes. Clonogenic myelo id progenitors (CFU-GM) were grown in semi-solid medium to measure their fr equency; the proliferative capacity of myeloid progenitors was measured by replating colonies and observing secondary colony formation. We found that the frequency of CFU-GM in normal marrow increased and their proliferative capacity decreased exponentially with age. The proliferative capacity of CF U-GM in normal blood also decreased exponentially with age. This relationsh ip extrapolated back to the levels of proliferation measured for cord blood CFU-GM (age = 0). The proliferative capacities of CFU-GM from children wit h bone marrow failure syndromes were severely reduced compared with age-mat ched reference values. These results indicate that a decline in haemopoieti c progenitor cell function begins at birth and continues throughout life. T his decline may occur prematurely in childhood marrow failure syndromes wit h a predisposition to leukaemia.