title: Shift from Rh-positive to Rh-negative phenotype caused by a somatic mutation within the RHD gene in a patient with chronic myelocytic leukaemia.
abstract: 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 Ph1 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 a 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 out 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.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Chérif-Zahar
authors.forename: V
authors.initials: V
authors.lastname: Bony
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.forename: P
authors.initials: P
authors.lastname: Gane
authors.forename: V
authors.initials: V
authors.lastname: Raynal
authors.forename: D
authors.initials: D
authors.lastname: Goosens
authors.forename: J S
authors.initials: JS
authors.lastname: Laursen
authors.forename: K
authors.initials: K
authors.lastname: Varming
authors.forename: C
authors.initials: C
authors.lastname: Jersild
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D004900:Erythroblasts / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood*; D008214:Lymphocytes / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012204:Rh-Hr Blood-Group System / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen