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Early evaluation of natural killer activity in post-transplant acute myeloid leukemia patients.

机译:移植后急性髓性白血病患者中自然杀伤活性的早期评估。

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The focus of this study was to investigate NK cell reconstitution early after hematopoietic stem cell transplantation (HSCT). We were particularly interested in acute myeloid leukemia (AML) since patients with this disease may display an altered NK cell function. The function and the phenotype of donor-derived NK cells obtained from 35 allografted patients 30 and 60 days after HSCT for AML or other-than-AML hematological malignancies has been assessed. NK functional status was investigated by measuring the degranulation capacity (externalization of CD107a) of NK cells against human K562. We also concomitantly determined the concentration of selected cytokines known to modulate NK function and/or receptor expression. At day 30, donor-derived AML and non-AML NK cells could efficiently degranulate when exposed to leukemic K562 targets. At day 60, we observed a reduced NK degranulation potential in AML patients only. Decreased NK activity in AML patients was concomitant to NKp46 and NKp30 down-regulation. AML NK cells were chronically exposed to low IL-2 levels following HSCT. TGF-beta(1) was undetectable in all patients. In AML, the functional activity of donor-derived NK cells is remarkable at day 30 but may strongly decrease two months after HSCT. Therefore, in this condition, early NK immune-modulation might improve HSCT outcome.
机译:这项研究的重点是研究造血干细胞移植(HSCT)后早期NK细胞的重建。我们对急性髓细胞性白血病(AML)特别感兴趣,因为患有这种疾病的患者可能表现出NK细胞功能改变。已评估了从35例HSCT术后30天和60天同种异体移植患者获得的AML或其他非AML血液系统恶性肿瘤的供体来源NK细胞的功能和表型。通过测量NK细胞对人K562的脱粒能力(CD107a的外部化)来研究NK的功能状态。我们还同时确定了已知可调节NK功能和/或受体表达的所选细胞因子的浓度。在第30天,暴露于白血病K562靶标时,供体来源的AML和非AML NK细胞可以有效地脱粒。在第60天,我们仅在AML患者中观察到NK脱颗粒的可能性降低。 AML患者的NK活性降低与NKp46和NKp30下调同时发生。 HSCT后,AML NK细胞长期暴露于低IL-2水平。在所有患者中均未检测到TGF-beta(1)。在AML中,供体来源的NK细胞的功能活性在第30天显着,但可能在HSCT后两个月急剧下降。因此,在这种情况下,早期的NK免疫调节可能会改善HSCT结果。

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