title: Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy.
abstract: Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3-4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with <80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.
authors.affiliation: HLA Laboratory, EFS Rhône Alpes, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Dubois
authors.forename: F
authors.initials: F
authors.lastname: Sloan-Béna
authors.forename: A
authors.initials: A
authors.lastname: Cesbron
authors.forename: B G
authors.initials: BG
authors.lastname: Hepkema
authors.forename: K
authors.initials: K
authors.lastname: Gagne
authors.forename: S
authors.initials: S
authors.lastname: Gimelli
authors.forename: D
authors.initials: D
authors.lastname: Heim
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: M
authors.initials: M
authors.lastname: Drouet
authors.forename: S
authors.initials: S
authors.lastname: Jendly
authors.forename: J
authors.initials: J
authors.lastname: Villard
authors.forename: J-M
authors.initials: JM
authors.lastname: Tiercy
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization; D003937:Diagnosis, Differential; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D006680:HLA Antigens