Loss of heterozygosity, a frequent but a non-exclusive mechanism responsible for HLA dysregulation in non-Hodgkin's lymphomas

British Journal of Haematology
B DrenouLaurence Amiot

Abstract

The frequent alteration of human leucocyte antigen (HLA) class I molecule expression observed in non-Hodgkin's lymphomas (NHL), similarly to solid tumours, has been reported to favour tumoral escape from the immune system. In order to identify the underlying mechanisms, we analysed 15 HLA defective NHL including partial (n = 10) and total class I (n = 5) loss, as well as HLA class II defects (n = 5). The HLA defect concerned HLA-A and -B antigens in 14 of 15 cases. In the cases with partial defect, the use of specific allelic monoclonal antibodies detected a defect of both alleles of A or B loci in six of seven tested cases. Allelic reverse transcription polymerase chain reaction (RT-PCR) demonstrated defects in six of nine cases, including four alterations of both A and B mRNA alleles. Real-time quantitative RT-PCR (RQ-PCR) did not detect the HLA-DR transcript in the two negative HLA-DR lymphomas, contrasting with the presence of CMH II transactivator (CIITA) transcript. Loss of heterozygosity (LOH) was detected in nine of 14 cases through variable pattern of nine microsatellites markers of the HLA locus. Taken together, these findings demonstrate the complexity and the variability of the mechanisms underlying HLA protein defi...Continue Reading

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Citations

Jan 22, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M TestoniF Bertoni
Apr 26, 2014·Frontiers in Immunology·Mir Munir A RahimAndrew P Makrigiannis
May 31, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arjan DiepstraSibrand Poppema
Aug 22, 2014·Journal of Cellular Biochemistry·Faisal F Y RadwanAzizul Haque
Sep 24, 2020·Leukemia & Lymphoma·Chantana PolprasertPonlapat Rojnuckarin
Jul 4, 2020·Cancer Discovery·Daisuke EnnishiDavid W Scott
Apr 13, 2021·Frontiers in Oncology·Benedetta ApollonioAlan G Ramsay
Jun 1, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M TestoniF Bertoni

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