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Toll 样受体(TLR2 和 TLR4)在急性髓系白血病患者中的临床意义。

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients.

机构信息

Hematology Unit, Department of Clinical pathology, Mansoura Faculty of Medicine, Mansoura University, Egypt.

Hematology Unit, Mansoura University Oncology Center, Mansoura University, Egypt.

出版信息

Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3177-3183. doi: 10.31557/APJCP.2020.21.11.3177.

DOI:10.31557/APJCP.2020.21.11.3177
PMID:33247673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8033142/
Abstract

BACKGROUNDS

Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient's outcome.

SUBJECTS AND METHODS

Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects.

RESULTS

No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis.

CONCLUSION

TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.
.

摘要

背景

Toll 样受体 2;4(TLR2;4)是先天免疫的重要组成部分,在对各种微生物的免疫监测和免疫反应中发挥重要作用。本研究旨在探讨 TLR2 和 TLR4 多态性与获得严重感染的风险之间的关系,并探讨其对 AML 患者预后的影响。

方法

采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析 120 例 AML 患者和 100 例健康对照者 TLR2(Arg753Gln)和 TLR4(Asp299Gly 和 Thr399Ile)的 3 个 SNP。

结果

健康对照组与 AML 患者 TLR2 Arg753Gln、TLR4 Asp299Gly 和 TLR4 Thr399Ile 多态性的基因型或等位基因频率无显著性差异(所有 P>0.05)。120 例研究 AML 患者中有 110 例(91.7%)出现中性粒细胞减少性发热。120 例患者中有 20 例(16.7%)发生脓毒症和肺炎。与其他基因型和等位基因相比,TLR2 Arg753Gln:AG 基因型、A 等位基因和 TLR4 Asp299Gly:CT 基因型和 C 等位基因与败血症的发生相关。此外,TLR2(Arg753Gln)GG 多态性与最短总生存期(OS)和最短无病生存期(DFS)显著相关;而 TLR4 多态性仅影响 DFS,而不影响 OS。在 AML 患者中,TLR2 Arg753Gln 基因多态性与败血症的高易感性相关,而 TLR4(Asp299Gly 和 Thr399Ile)基因多态性与肺炎和败血症的高易感性相关。

结论

TLR2 Arg753Gln(AG; GG 基因型)多态性与最短的 OS 和 DFS 相关。此外,还记录了 TLR2 多态性、TLR4 Arg753Gln 多态性与 AML 患者严重感染风险之间的显著关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/a35996a9ca84/APJCP-21-3177-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/a8314b770033/APJCP-21-3177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/2ba3c3d45c54/APJCP-21-3177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/e284e2a2ea53/APJCP-21-3177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/448942112851/APJCP-21-3177-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/32147602655a/APJCP-21-3177-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/a35996a9ca84/APJCP-21-3177-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/a8314b770033/APJCP-21-3177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/2ba3c3d45c54/APJCP-21-3177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/e284e2a2ea53/APJCP-21-3177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/448942112851/APJCP-21-3177-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/32147602655a/APJCP-21-3177-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d18/8033142/a35996a9ca84/APJCP-21-3177-g006.jpg

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