SHIFT FROM RH-POSITIVE TO RH-NEGATIVE PHENOTYPE CAUSED BY A SOMATIC MUTATION WITHIN THE RHD GENE IN A PATIENT WITH CHRONIC MYELOCYTIC-LEUKEMIA

We report a female patient whose Rh phenotype shifted from RhD-positiv e to RhD-negative over a 3-year period (1991-94), during which time sh e was treated with mastectomy (1992) and local irradiation for a low-g rade recurrent breast cancer. She was diagnosed with chronic myeloid l eukaemia in 1994, and has since then received chemotherapy, The patien t was repeatedly typed as O, RhD-positive between 1965 and 1991 and wa s repeatedly found RhD-negative after 1994. Bcr-Abl transcripts typica l of Phl chromosome were detected, Molecular analysis indicated that t he patient was heterozygous at the RH locus, carrying one haplotype in which the RHD gene exhibited a single nucleotide deletion (G600) resu lting 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 erythr oblasts indicated that the G600 deletion was restricted to the myeloid lineage, No modification of other blood group antigens could be detec ted, These findings suggest a somatic mutation which most probably occ urred in a stem cell common to the myeloid lineage.