Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts

Cancer Sci. 2007 Jan;98(1):102-8. doi: 10.1111/j.1349-7006.2006.00356.x.

Abstract

Loss or down-regulation of human leukocyte antigen (HLA) class I expression has been demonstrated in a variety of solid tumors. To date, such altered HLA expression has not been studied extensively in freshly isolated leukemic blasts. If it occurs, leukemic cells could escape T-cell surveillance as a consequence. Genotypes of nine leukemic cell lines were determined using a polymerase chain reaction for HLA classes I and II. Cells were also examined for HLA beta2-microglobulin, and allele-specific HLA protein expression using flow cytometry. Next, 44 samples of freshly isolated leukemic blasts from 43 patients with malignant hematological diseases were examined for allele-specific HLA expression using flow cytometry. Microsatellite analysis was performed to determine heterozygosity in the HLA region on chromosome 6. Genotype analysis for HLA class I together with microsatellite analysis demonstrated loss of HLA haplotype in HL-60 cells. No loss of HLA haplotype was observed in 44 samples of freshly isolated leukemic blasts. As reported previously, flow cytometric analysis rarely demonstrated loss or down-regulation of HLA expression at initial diagnosis (3/39; 7.7%); however, this was evident in two of five cases in relapse (40.0%), which contrasts with previous reports. In one patient with acute leukemia, HLA-A2 cell surface expression was present at initial diagnosis, lost at relapse, and completely restored after 48 h of culture in the presence of interferon-gamma. These results suggest loss of allele-specific HLA expression may be involved in the pathogenesis of relapse in patients with leukemia. The findings should be valuable in designing new strategies for clinical immunotherapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blast Crisis / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Gene Expression
  • Genotype
  • Haplotypes
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Loss of Heterozygosity*
  • Lymphoproliferative Disorders / genetics*
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Polymerase Chain Reaction

Substances

  • Histocompatibility Antigens Class I