IDIOPATHIC MACROCYTIC ANEMIA IN THE AGED - MOLECULAR AND CYTOGENETIC FINDINGS

Macrocytosis in the elderly is often caused by abnormalities of haemat ological stem cell differentiation. In this study, a group of elderly patients was analysed for four molecular and cell biological parameter s. The aim of the study was to screen elderly patients with idiopathic macrocytic anaemia or MDS for a set of alterations which are related to haematological dysplasia, The analyses used were: DNA-methylation a t the calcitonin A gene 5'-area, NRAS point mutations at codons 12 and 13, in vitro colony formation of peripheral blood progenitor cells an d cytogenetics of bone marrow cells, The results show that a significa nt portion of elderly patients with idiopathic macrocytosis have one o r more of the abnormalities analysed, Hypermethylation of the calciton in A gene 5'-area at the chromosome 11 band p15 is relatively common ( 7/15). Chromosomal aberrations (3/12) and NRAS oncogene point mutation s (0/15) were rare findings. In vitro culture of erythroid progenitor cells was relatively frequently abnormal (7/15). Eight of our nine mac rocytic patients who did not fulfill the FAB criteria for MDS had at l east one of the alterations studied; this suggests that these patients might represent early phases of a stem cell disorder.