Abstract
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.
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