Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy
- 14 March 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 26 (9), 2079-2085
- https://doi.org/10.1038/leu.2012.68
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 remissionKeywords
This publication has 19 references indexed in Scilit:
- Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell TransplantationTransplantation and Cellular Therapy, 2011
- Short tandem repeat and human leukocyte antigen mutations or losses confound engraftment and typing analysis in hematopoietic stem cell transplantsHuman Immunology, 2011
- HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillanceLeukemia, 2011
- De novo rates and selection of large copy number variationGenome Research, 2010
- Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantationBlood, 2010
- Loss of Mismatched HLA in Leukemia after Stem-Cell TransplantationNew England Journal of Medicine, 2009
- Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemiaBlood, 2008
- Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotypeLeukemia & Lymphoma, 2008
- Loss or down‐regulation of HLA class I expression at the allelic level in freshly isolated leukemic blastsCancer Science, 2006
- Implications for immunosurveillance of altered HLA class I phenotypes in human tumoursImmunology Today, 1997