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

Kozo Masuda, Akio Hiraki, Nobuharu Fujii, Toshiyuki Watanabe, Motoyuki Tanaka, Kosei Matsue, Yoichiro Ogama, Mamoru Oouchida, Kenji Shimizu, Kazuma Ikeda, Mitsune Tanimoto

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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 languageEnglish
Pages (from-to)102-108
Number of pages7
JournalCancer Science
Volume98
Issue number1
DOIs
Publication statusPublished - Jan 2007

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HLA Antigens
Down-Regulation
Alleles
Recurrence
Microsatellite Repeats
Haplotypes
Flow Cytometry
Leukemia
Genotype
Chromosomes, Human, Pair 6
Hematologic Diseases
HL-60 Cells
varespladib methyl
Immunotherapy
Interferons

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 journalArticle

Masuda, K, Hiraki, A, Fujii, N, Watanabe, T, Tanaka, M, Matsue, K, Ogama, Y, Oouchida, M, Shimizu, K, Ikeda, K & Tanimoto, M 2007, 'Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts', Cancer Science, vol. 98, no. 1, pp. 102-108. https://doi.org/10.1111/j.1349-7006.2006.00356.x
Masuda, Kozo ; Hiraki, Akio ; Fujii, Nobuharu ; Watanabe, Toshiyuki ; Tanaka, Motoyuki ; Matsue, Kosei ; Ogama, Yoichiro ; Oouchida, Mamoru ; Shimizu, Kenji ; Ikeda, Kazuma ; Tanimoto, Mitsune. / Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts. In: Cancer Science. 2007 ; Vol. 98, No. 1. pp. 102-108.
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