Detection of an acquired mutation in an HLA-A∗03 allele impairing gene expression in leukemia cells of a patient with all

Smith, Anajane G.; Sprague, Maggie; Peterson, Paula; Worley, L; McKinney, Susan; Warnock, Sandra

doi:10.1016/s0198-8859(02)00482-2

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“…Although other chromosomes are more frequently affected, the short arm of chromosome 6 has been shown to exhibit LOH in both MDS/secondary AML and primary AML. Anecdotal cases reported by several investigators describe detection of LOH in human leukocyte antigen (HLA) genes of patients with hematological malignancy through HLA typing prior to hematopoietic cell transplant (3)(4)(5)(6)(7)(8)(9)(10)(11). Loss of HLA expression associated with LOH has also been reported in patients with both solid tumors (12,13) and leukemia (14).…”

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confidence: 99%

Somatic mutations in the HLA genes of patients with hematological malignancy

et al. 2012

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Somatic mutations and genomic alterations are frequent events in the clonal evolution of hematologic malignancies. Recent studies have reported copy neutral loss of heterozygosity (LOH) for the mismatched human leukocyte antigen (HLA) haplotype in patients relapsed after haploidentical hematopoietic cell transplantation (HCT) for a hematologic malignancy. Herein, we report 15 cases of somatic mutations in the HLA genes of patients with a variety of hematologic diseases, including acute myelogenous leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, and non-Hodgkin's lymphoma, encountered at our institute over the past decade. While two of the cases were identified in patient relapse specimens collected post-HCT, 13 cases were found in peripheral blood specimens submitted for HLA typing prior to transplantation. Ten patients exhibited acquired LOH for all or part of one HLA haplotype. Five other cases involved somatic mutations in the nucleotide sequences of common HLA-A or HLA-B alleles. Since they are not systematically evaluated prior to HCT, acquired mutations in HLA genes are likely under reported. Beyond the implications for accurate HLA typing and donor selection, alternations that result in the loss of HLA expression may allow escape from immune surveillance and adversely impact transplant outcome.

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