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Leukemia specific loss of heterozygosity of MHC in a CLL patient: Disease state impacts timing of confirmatory typing

Departments of Pathology and Laboratory Medicine University of Rochester Medical Center and the Wilmot Cancer Center, Rochester, NY. Electronic address: .
Human immunology (Impact Factor: 2.28). 10/2012; 74(1). DOI: 10.1016/j.humimm.2012.10.003
Source: PubMed

ABSTRACT A 63 year old white male with refractory B-CLL presented for allogeneic HSCT evaluation; HLA typing was performed on PBL at time of WBC= 53K, ALC= 47K and revealed homozygosity at Class I locus and heterozygosity at Class II locus. Two siblings were full mismatches with the recipient and an unrelated search initiated. The patient was treated with Fludaribine and Rituxan complicated by aplastic anemia and bacteremia. Prior to transplant, confirmatory typing performed on PB revealed two full haplotypes at Class I and II. Sample identification error and the presence of third party lymphocyte engraftment as a result of prior red cell or granulocyte transfusion(s) were ruled out by STR analysis of 8 loci of all samples, T and B cells from cryopreserved PB at blast crisis were HLA typed independently. T cell typing yielded both complete haplotypes (genotype verified by offspring HLA typing); B cells typed for homozygous haplotype indicating loss of heterozygosity of MHC locus. Microarray based comparative genomic hybridization of tumor cells confirmed LOH at 6p.

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    • "In addition, loss of HLA heterozygosity was also described prior to any treatment [4, 6–10] in malignant cells, which might be a serious confounder in a patient's HLA typing. Despite its vital importance, copy number neutral loss of heterozygosity is easily missed by standard methods. "
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