Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts.
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.
Masuda
Kozo
K
Department of Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Hiraki
Akio
A
Fujii
Nobuharu
N
Watanabe
Toshiyuki
T
Tanaka
Motoyuki
M
Matsue
Kosei
K
Ogama
Yoichiro
Y
Ouchida
Mamoru
M
Shimizu
Kenji
K
Ikeda
Kazuma
K
Tanimoto
Mitsune
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005838:Genotype; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016133:Polymerase Chain Reaction
D015395:Histocompatibility Antigens Class I