Patients successfully treated for
lymphoma by conventional cytotoxic
therapy are at increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia. In this study we have investigated a group of haematologically normal females in remission from
lymphoma for evidence of clonal haemopoiesis as a possible marker for the development of clonal haemopoietic disorders. Unilateral X-inactivation, and hence clonality, can be determined in females heterozygous for X-linked restriction fragment length polymorphisms by differences in methylation between active and inactive X-chromosomes. We have studied methylation patterns at the DXS255 locus and the
phosphoglycerate kinase (PGK) gene in 25 females in remission from
lymphoma and compared them to 35 normal females. Unilateral X-inactivation was detected in 4/15 patients in remission from
lymphoma versus 2/27 normals at the DXS255 locus and in 4/13 treated
lymphoma patients versus 0/11 normals at the PGK locus. Six individuals were analysed by both techniques with complete concordance. Unilateral X-inactivation was more common following cytotoxic
therapy for
lymphoma (7/25) than in normals (2/35) (p < 0.025) and in the
lymphoma cohort was associated with increasing time from the end of
therapy (p = 0.03). Patients in remission from
lymphoma have an increased incidence of clonal haemopoiesis compared to normal individuals. This may be due to either the clonal expansion of an abnormal genetically damaged stem cell or a variation of normal haemopoiesis. Prospective studies will establish whether this finding is associated with an increased risk of developing treatment-related myelodysplasia and acute myeloid leukaemia.