Analysis of HLA class Ia transcripts in human leukaemias

Immunogenetics. 2005 Sep;57(8):579-89. doi: 10.1007/s00251-005-0018-9. Epub 2005 Sep 29.


Several leukaemia-specific antigens have been discovered in the recent past, which raised the possibility for T-cell-based immunotherapy for leukaemia. However, failure of such approaches involving interleukin-2 and/or T-cell-based immunotherapy indicated the importance of investigation of the human leucocyte antigen (HLA) status of the haematopoietic malignant cells. Considerable number of reports indicate that both HLA class I and class II are down-regulated in different cases of leukaemias, enabling them to evade immuno-surveillance. However, locus-specific down-regulation in leukaemia has not been widely investigated, although majority of cytotoxic T lymphocyte (CTL) responses are modulated by HLA-A and HLA-B, whereas expression of only HLA-C is unable to block natural killer (NK)-cell-mediated cytotolysis. Therefore, using RT-PCR, we have investigated the HLA class I transcriptional expression in a locus-specific manner, along with HLA-associated accessory molecules beta2-microglobulin and transporter-associated antigen processing molecule (TAP1). Our data suggest that in several newly diagnosed untreated leukaemic patients, HLA-C and beta2-microglobulin are expressed, but not the locus HLA-A or -B. Moreover, TAP1 and beta2-microglobulin were observed to be down-regulated in a number of cases of leukaemia. Our flow cytometric analysis of HLA-ABC also indicates a decrease in mean fluorescent intensity but no complete loss in surface expression of HLA class Ia on the leukaemic cells. Therefore, the observed low surface expression of HLA-ABC may be due to the down-regulation of transcription of HLA-A or -B itself and/or transcriptional suppression of the accessory molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-C Antigens / genetics
  • HLA-DR Antigens / genetics
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Leukemia / genetics
  • Leukemia / immunology*
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • beta 2-Microglobulin / genetics


  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • RNA, Messenger
  • TAP1 protein, human
  • beta 2-Microglobulin