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[ASCO2015]KIR基因与MDS的相关性

2015-05-26 17:42 阅读:519 来源:医脉通 作者:林夕 责任编辑:林夕
[导读] 骨髓增生异常综合征(MDS)表现为连续的损伤髓系的无性系造血功能障碍,其特征为血细胞减少,发育异常。MDS是根据国际预后评分系统(IPSS)进行风险分层的。

    骨髓增生异常综合征(MDS)表现为连续的损伤髓系的无性系造血功能障碍,其特征为血细胞减少,发育异常。MDS是根据国际预后评分系统(IPSS)进行风险分层的。这些疾病的主要临床并发症——尤其是在高危组中——是进展为急性髓系白血病(AML)的可能性。证据是累积在对MDS敏感/耐药中发挥重要作用的基因因素。(摘要ID:7001)在这一方面,活化杀伤细胞免疫球蛋白样受体(KIR)基因在自然杀伤细胞中的表达尤其引人关注。人类遗传的六种不同活化的KIR基因数量可能不同。但是我们对这种基因变体对人类发生MDS的先天敏感性或耐药性的作用知之甚少。

    【方法】

    研究者通过病例对照研究解决这一问题,研究纳入180名MDS患者(120名IPSS评分高,60名IPSS评分低)和117名健康供者。在病例组和对照组患者中收集DNA样本,使用PCR分析活化KIR基因。

    【结果】

    结果显示,高危MDS患者的活化KIR基因数量显著低于低危MDS患者(P = 0.009)和对照组患者(P = 0.00001)。低危MDS患者的活化KIR基因数量低于对照组患者(P = 0.04)。重要的是,每种附加活化KIR基因的遗传对预防高危MDS的发生有保护作用(RR 0.7, P <0.001)。

    【结论】

    研究结果表明,活化KIR基因的数量高可以预防MDS,而且一旦发生这种疾病,KIR基因数量低可导致高危疾病。因此,这项研究为成人MDS的发病机理提供了新的见解,形成一种使用NK细胞控制疾病的新型免疫疗法,防止MDS进展为高危疾病,甚至发展为AML.

    编译自:Association between KIR genes and risk of MDS. ASCO. 2015.5

    英文摘要:

    Background: Myelodysplastic syndrome (MDS) represents a spectrum of clonal hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and dysplastic features. MDS is risk-stratified according to International Prognostic Scoring System (IPSS) scores. The major clinical complication inthese disorders, especially in the high-risk group, is the potential to evolveinto acute myeloid leukemia (AML)。 Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to MDS. Inthis regard, activating killer-cell immunoglobulin-like receptor (KIR) genes expressed in natural killer cells (NK cells) are of particular interest. Humans may inherit different numbers of the six distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to develop MDS.

    Methods: We addressed this issue by performing a case-control study involving 180 MDS patients (120 with high IPSS, 60 with low IPSS) and 117 healthy donors. DNA samples were collected in both cases and controls and **ysis of activating KIR genes was performed using PCR.

    Results: Ourresults showed that patients with high-risk MDS had significantly lower numbers of activating KIR genes compared to patients with low-risk MDS (P = 0.009) and compared to healthy controls (P = 0.00001)。 Patients with low-risk MDS also had fewer activating KIR genes when compared to controls (P = 0.04)。 Importantly,inheritance of each additional activating KIR gene had a protective effectagainst development of high risk MDS (RR 0.7, P < 0.001)。

    Conclusions:These results suggest that inheritance of a higher number of activating KIR genes is protective against MDS, and that once the disease develops, harboring a lower number of KIR genes is associated with higher risk disease. Hence, our study provides novel insights concerning the pathogenesis of MDS in **s and has implications for the development of new immunotherapies using NK cells with potential of controlling the disease and preventing progression to high risk disease and eventually to AML.


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