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您所在的位置:首頁(yè) > 血液科醫學(xué)進(jìn)展 > [ASCO2015]KIR基因與MDS的相關(guān)性

[ASCO2015]KIR基因與MDS的相關(guān)性

2015-05-26 17:42 閱讀:1914 來(lái)源:醫脈通 作者:林* 責任編輯:林夕
[導讀] 骨髓增生異常綜合征(MDS)表現為連續的損傷髓系的無(wú)性系造血功能障礙,其特征為血細胞減少,發(fā)育異常。MDS是根據國際預后評分系統(IPSS)進(jìn)行風(fēng)險分層的。

    骨髓增生異常綜合征(MDS)表現為連續的損傷髓系的無(wú)性系造血功能障礙,其特征為血細胞減少,發(fā)育異常。MDS是根據國際預后評分系統(IPSS)進(jìn)行風(fēng)險分層的。這些疾病的主要臨床并發(fā)癥——尤其是在高危組中——是進(jìn)展為急性髓系白血病(AML)的可能性。證據是累積在對MDS敏感/耐藥中發(fā)揮重要作用的基因因素。(摘要ID:7001)在這一方面,活化殺傷細胞免疫球蛋白樣受體(KIR)基因在自然殺傷細胞中的表達尤其引人關(guān)注。人類(lèi)遺傳的六種不同活化的KIR基因數量可能不同。但是我們對這種基因變體對人類(lèi)發(fā)生MDS的先天敏感性或耐藥性的作用知之甚少。

    【方法】

    研究者通過(guò)病例對照研究解決這一問(wèn)題,研究納入180名MDS患者(120名IPSS評分高,60名IPSS評分低)和117名健康供者。在病例組和對照組患者中收集DNA樣本,使用PCR分析活化KIR基因。

    【結果】

    結果顯示,高危MDS患者的活化KIR基因數量顯著(zhù)低于低危MDS患者(P = 0.009)和對照組患者(P = 0.00001)。低危MDS患者的活化KIR基因數量低于對照組患者(P = 0.04)。重要的是,每種附加活化KIR基因的遺傳對預防高危MDS的發(fā)生有保護作用(RR 0.7, P <0.001)。

    【結論】

    研究結果表明,活化KIR基因的數量高可以預防MDS,而且一旦發(fā)生這種疾病,KIR基因數量低可導致高危疾病。因此,這項研究為成人MDS的發(fā)病機理提供了新的見(jiàn)解,形成一種使用NK細胞控制疾病的新型免疫療法,防止MDS進(jìn)展為高危疾病,甚至發(fā)展為AML.

    編譯自: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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