Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia
| Autor: | Shinji Nakao, Hiroyuki Maruyama, Seishi Ogawa, Hirohito Yamazaki, Koichi Kashiwase, Kana Maruyama, Yoshitaka Zaimoku, Aiko Sato-Otsubo, Takamasa Katagiri, Ken Ishiyama, Hidetoshi Inoko, Kohei Hosokawa, Takashi Shiina |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Cancer Research Gene Expression Severity of Illness Index 0302 clinical medicine Gene Frequency Leukocytes Child Aged 80 and over education.field_of_study Anemia Aplastic Hematology Middle Aged Flow Cytometry Prognosis HLA-A Haematopoiesis Phenotype Treatment Outcome 030220 oncology & carcinogenesis Child Preschool Cyclosporine Female Stem cell Adult Adolescent DNA Copy Number Variations Genotype Anemia Population Biology Polymorphism Single Nucleotide 03 medical and health sciences Young Adult Genetics medicine Humans Clinical significance Cell Lineage education Molecular Biology Allele frequency Alleles Genetic Association Studies Aged Antilymphocyte Serum HLA-A Antigens Bone marrow failure Cell Biology medicine.disease Immunology Biomarkers 030215 immunology |
| Zdroj: | Experimental hematology. 44(10) |
| ISSN: | 1873-2399 |
| Popis: | To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number-neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA),weused a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes(HLA-LLs) in 144 AA patients. HLA-LLs, accounting for0.2–99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patientsand in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL+patients were granulocytes (Gs), monocytes (Ms), Bcells (Bs), and Tcells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survivalrate (100%) in 8 newly diagnosed HLA-LL+ patients were significantly higher than in 23 HLA-LL− patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients. © 2016 ISEH - International Society for Experimental Hematology Embargo Period 12 months |
| Databáze: | OpenAIRE |
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