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 β2-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-γ. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 102-108 |
| Number of pages | 7 |
| Journal | Cancer Science |
| Volume | 98 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2007 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts. / Masuda, Kozo; Hiraki, Akio; Fujii, Nobuharu; Watanabe, Toshiyuki; Tanaka, Motoyuki; Matsue, Kosei; Ogama, Yoichiro; Oouchida, Mamoru; Shimizu, Kenji; Ikeda, Kazuma; Tanimoto, Mitsune.
In: Cancer Science, Vol. 98, No. 1, 01.2007, p. 102-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts
AU - Masuda, Kozo
AU - Hiraki, Akio
AU - Fujii, Nobuharu
AU - Watanabe, Toshiyuki
AU - Tanaka, Motoyuki
AU - Matsue, Kosei
AU - Ogama, Yoichiro
AU - Oouchida, Mamoru
AU - Shimizu, Kenji
AU - Ikeda, Kazuma
AU - Tanimoto, Mitsune
PY - 2007/1
Y1 - 2007/1
N2 - 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 β2-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-γ. 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.
AB - 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 β2-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-γ. 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.
UR - http://www.scopus.com/inward/record.url?scp=33751313854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751313854&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2006.00356.x
DO - 10.1111/j.1349-7006.2006.00356.x
M3 - Article
C2 - 17083564
AN - SCOPUS:33751313854
VL - 98
SP - 102
EP - 108
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -