Hong Wang1,2, Mingqiang Hua1, Shukang Wang3, Jie Yu1, Chen Chen1, Xueyun Zhao1, Chen Zhang1, Chaoqin Zhong1, Ruiqing Wang1, Na He1, Ming Hou1, Daoxin Ma4. 1. Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China. 2. Department of Hematology, Zibo Central Hospital, Zibo, Shandong, People's Republic of China. 3. Department of Epidemiology and Biostatistics, School of Public Health, Shandong University, Jinan, People's Republic of China. 4. Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China. daoxinma@sdu.edu.cn.
Abstract
BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION: IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.
BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AMLpatients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION: IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.
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