title: Idiopathic macrocytic anaemia in the aged: molecular and cytogenetic findings.
abstract: Macrocytosis in the elderly is often caused by abnormalities of haematological stem cell differentiation. In this study, a group of elderly patients was analysed for four molecular and cell biological parameters. 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 at the calcitonin A gene 5'-area, NRAS point mutations at codons 12 and 13, in vitro colony formation of peripheral blood progenitor cells and cytogenetics of bone marrow cells. The results show that a significant portion of elderly patients with idiopathic macrocytosis have one or more of the abnormalities analysed. Hypermethylation of the calcitonin A gene 5'-area at the chromosome 11 band p15 is relatively common (7/15). Chromosomal aberrations (3/12) and NRAS oncogene point mutations (0/15) were rare findings. In vitro culture of erythroid progenitor cells was relatively frequently abnormal (7/15). Eight of our nine macrocytic patients who did not fulfill the FAB criteria for MDS had at least one of the alterations studied; this suggests that these patients might represent early phases of a stem cell disorder.
authors.affiliation: Department of Internal Medicine, Helsinki City Hospital, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Anttila
authors.forename: J
authors.initials: J
authors.lastname: Ihalainen
authors.forename: A
authors.initials: A
authors.lastname: Salo
authors.forename: M
authors.initials: M
authors.lastname: Heiskanen
authors.forename: E
authors.initials: E
authors.lastname: Juvonen
authors.forename: A
authors.initials: A
authors.lastname: Palotie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000748:Anemia, Macrocytic / Q000235:genetics / Q000473:pathology*; D002116:Calcitonin / Q000235:genetics; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008297:Male; D008745:Methylation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology*; D017354:Point Mutation
chemical_list: D002116:Calcitonin; D004247:DNA