Shift from Rh-positive to Rh-negative phenotype caused by a somatic mutation within the RHD gene in a patient with chronic myelocytic leukaemia

We report a female patient whose Rh phenotype shifted from RhD-positive to RhD-negative over a 3-year period (1991-94), during which time she was treated with mastectomy (1992) and local irradiation for a low-grade recurrent breast cancer. She was diagnosed with chronic myeloid leukaemia in 1994, and has since then received chemotherapy, The patient was repeatedly typed as O, RhD-positive between 1965 and 1991 and was repeatedly found RhD-negative after 1994. Bcr-Abl transcripts typical of Phl chromosome were detected, Molecular analysis indicated that the patient was heterozygous at the RH locus, carrying one haplotype in which the RHD gene exhibited a single nucleotide deletion (G600) resulting in frameshift and premature stop codon, and a normal RHCE gene (allele Ce). The second haplotype contained only the RHCE gene (allele ce) and was normal, Further analysis carried put on total leucocytes, purified neutrophils, EBV-lymphoblastoid cell line and cultured erythroblasts indicated that the G600 deletion was restricted to the myeloid lineage, No modification of other blood group antigens could be detected, These findings suggest a somatic mutation which most probably occurred in a stem cell common to the myeloid lineage.