Immunorelated gene polymorphisms associated with acute myeloid leukemia
Immunorelated gene polymorphisms associated with acute myeloid leukemia
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急性髓系白血病的免疫相关基因多态性
DOI：
10.1111/cei.13446
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发表时间：
2020-06-02
影响因子：
4.6
通讯作者：
Ma, D.
中科院分区：
文献类型：
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作者：
Liu, Q.;Hua, M.;Ma, D.
尽管急性髓性白血病（AML）的发病机制尚不清楚，但越来越多的证据表明免疫反应在其发病过程中起着至关重要的作用。在这里，我们研究了免疫相关基因的21个单核苷酸多态性（snp），包括细胞因子[白细胞介素(IL)-2, IL-4, IL-9, IL- 12a, IL-22，干扰素（ifn - α）和转化生长因子(TGF)- β 1]，转录调节基因（TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3， FOXP3和IRF4）和其他基因（IL2RA, IL6R， NFKBIA）在269名AML住院患者和200名健康对照中的参与。此外，我们还分析了snp与临床特征之间的关系。在Sequenom MassARRAY iPLEX平台上进行免疫相关SNP基因分型。健康对照的所有snp均符合Hardy-Weinberg平衡。所有最终p值均采用Bonferroni多重检验进行调整。我们的结果显示IL-22 （rs2227491）与白细胞（WBC）计数显著相关。转录信号传导激活因子5B (STAT-5B) （rs6503691）与AML患者复发性遗传异常密切相关。我们验证了年龄和细胞遗传学风险对总生存率（OS）的负独立影响。更重要的是，IL-12A （rs6887695）的GG基因型独立对AML预后有负面影响。此外，无论是共显性还是隐性模型，GG基因型中IL-12的相对表达量均降低。然而，上述snp与疾病易感性、危险分层和生存率之间没有相关性。我们的研究结果表明，免疫相关基因多态性与AML患者的预后相关，可能成为AML患者新的检查靶点。
Although the pathogenesis of acute myeloid leukemia (AML) is still unknown, accumulating evidence has revealed that immune response plays a vital part in the pathogenesis. Here, we investigated the involvement of 21 single nucleotide polymorphisms (SNPs) of immunorelated genes, including cytokines [interleukin (IL)-2, IL-4, IL-9, IL-12A, IL-22, interferon (IFN-alpha) and transforming growth factor (TGF)-beta 1], transcriptional regulatory genes (TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3, FOXP3 and IRF4) and others (IL2RA, IL6R, NFKBIA) in 269 AML in-patients and 200 healthy controls. Furthermore, we analyzed the relationship between the SNPs and clinical characteristics. Immunorelated SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. All the SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium. All final P-values were adjusted by Bonferroni multiple testing. Our results showed that IL-22 (rs2227491) was significantly associated with the white blood cell (WBC) counts. Signal transducer and activator of transcription 5B (STAT-5B) (rs6503691) showed a close relationship with the recurrent genetic abnormalities in patients with AML. We verified the negatively independent effect of age and risk of cytogenetics on overall survival (OS). More importantly, the GG genotype of IL-12A (rs6887695) showed a negative impact on AML prognosis independently. Furthermore, the relative expression of IL-12 was decreased in GG genotype, no matter under a co-dominant or recessive model. However, no correlation was observed between the SNPs mentioned above and disease susceptibility, risk stratification and survival. Our findings suggest that immunorelated gene polymorphisms are associated with prognosis in AML, which may perform as novel inspection targets for AML patients.