Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts
| Autor: | Mitsune Tanimoto, Mamoru Ouchida, Toshiyuki Watanabe, Nobuharu Fujii, Kozo Masuda, Kenji Shimizu, Kosei Matsue, Yoichiro Ogama, Kazuma Ikeda, Motoyuki Tanaka, Akio Hiraki |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Cancer Research Adolescent Genotype Down-Regulation Gene Expression Loss of Heterozygosity Human leukocyte antigen Biology Polymerase Chain Reaction Flow cytometry Loss of heterozygosity Cell Line Tumor medicine Humans Cytotoxic T cell Aged Aged 80 and over Acute leukemia medicine.diagnostic_test Histocompatibility Antigens Class I Haplotype General Medicine Middle Aged Flow Cytometry medicine.disease Lymphoproliferative Disorders Leukemia Haplotypes Oncology Immunology Female Neoplasm Recurrence Local Blast Crisis Microsatellite Repeats |
| Zdroj: | Cancer Science. 98:102-108 |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2006.00356.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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