Clonal evolution in human lymphoblast cultures

Abstract

We established lymphoblast cultures from normal females heterozygous for electrophoretic variants of glucose-6-phosphate dehydrogenase (G6PD), and the X-linked markers have permitted us to look at evolution of these cell populations in culture. The established cultures were phenotypically heterozygous at onset, having both of the mosaic cell populations resulting from X chromosome inactivation. However, by the tenth subculture, the population of cells no longer reflected the heterozygous genotype in 50% of the cultures, as only a single G6PD isozyme was expressed. The ultimate cell composition seems to be influenced by the initial composition, by the nature of alleles at heterozygous X-linked loci that may provide a growth advantage (or disadvantage), as well as by stochastic events. Our results show that lymphoblast cultures may not reflect the X-linked phenotype of the cells from which they were derived. The fate of such cultures seems to be evolution toward clonal cell populations.