RESUMO
MicroRNA (miR)-17-92a expression plays a crucial role in lymphocyte ontogeny. We therefore set out to determine miR-92a expression levels in peripheral blood lymphocytes from healthy subjects to ascertain any association between these levels and ageing. We found a positive correlation between the miR-92a expression level and the percentages of RO-CD8+CD27+ (P = 0.0046) and CD3+CD8+CD62L+ (P = 0.0011). This suggests that the majority of miR-92a of CD8+ T cells is derived from naïve cells, and the miR-92a expression level in CD8+ T cells declines progressively with age. These results indicate that the age-related attrition of naïve T cells is linked to a reduction of miR-92a in human T -lymphocytes. Therefore, we should careful attention when evaluating human miRNA levels in T lymphocytes to use normal control values.
RESUMO
BACKGROUND: We undertook a study to evaluate the clinical relevance of miR-92a in plasma obtained from non-Hodgkin's lymphoma (NHL) patients, because the miR-17-92 polycistronic miRNA cluster plays a crucial role in lymphomagenesis and affects neo-angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Plasma miR-92a values in NHL were extremely low (<5%), compared with healthy subjects (P<.0001), irrespective of lymphoma sub-type. The very low plasma level of miR-92a increased in the complete response (CR) phase but did not reach the normal range, and the plasma level was lower again in the relapse phase. Patients in CR or CR unconfirmed with a plasma miR-92a level of less than the cut-off level showed a significantly high relapse rate compared with patients with normalized plasma miR-92a level. CONCLUSIONS/SIGNIFICANCE: The current results therefore indicate that the plasma miR-92a value could be a novel biomarker not only for diagnosis but also for monitoring lymphoma patients after chemotherapy.
Assuntos
Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Análise Química do Sangue/métodos , Regulação para Baixo , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Masculino , MicroRNAs/análise , MicroRNAs/genética , Análise em Microsséries , Pessoa de Meia-Idade , Prognóstico , Risco , Estudos de Validação como AssuntoRESUMO
Donor killer immunoglobulin-like receptor (KIR) and KIR-ligand mismatch is considered vital in clarifying the mechanism of natural killer (NK) cell alloreactivity in hematopoietic stem cell transplantation (HSCT). In practical terms, however, it may be difficult to analyze the KIR genotype of donor cells directly as all donor cells are used for the transplant rather than for research purposes. To accurately estimate donor KIR genotype, we determined recipient KIR genotyping sequentially, at a minimum of two time points, using 19 KIR-specific primers in 10 patients who underwent HSCT. Among 10 patients, four had a KIR-ligand mismatch in the graft versus host direction. Sequential KIR genotyping showed the genotype changes at the time of engraftment (donor-derived) as well as relapse (recipient-derived). Our results highlight the utility of sequential KIR genotyping to better understand ligand-ligand, KIR-KIR, or ligand-KIR mismatches. Further studies, including a functional assay of NK cells may clarify the underlying mechanism of KIR ligand-donor KIR mismatch in HSCT.