Genetic Polymorphisms in NLRP3 Inflammasome-Associated Genes in Patients with B-Cell Non-Hodgkin’s Lymphoma

Liu, Zhi-He; Zhang, Lin; Jing, Fan-Jing; Xiao, Shuxin; Yan, Guoquan; Bian, Haiyan; Zhao, Xia

doi:10.2147/jir.s329090

Cited by 6 publications

(7 citation statements)

References 34 publications

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“…In either in vitro or in vivo experiments, administration of NLRP3 inhibitors caused amelioration of the disease burden in AML, DLBCL, GvHD, multiple myeloma, and sickle cell anemia [ 25 , 36 , 40 , 61 , 67 ]. Moreover, specific gene variants of the NLRP3 inflammasome were correlated with a susceptibility to developing lymphomas, ALL, CML, and possibly MM [ 24 , 38 , 45 , 47 , 48 ]. Altogether, these results show the potentially universal role of the NLRP3 in the pathogenesis of hematological diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, samples from newly diagnosed lymphoma patients showed significantly elevated mRNA levels of the IL-18 cytokine, the effector of the inflammasome pathway, compared with controls [ 23 ]. Moreover, examination of SNPs revealed that polymorphisms in the IL-18 gene might increase a patient’s susceptibility to developing DLBCL or follicular lymphoma (FL) [ 24 ], whereas specific SNPs in the CARD8 gene contribute to decreased survival [ 24 ]. Elevated IL-18 was detected in DLBCL patients and correlated positively with PD-L1 expression, a molecule impeding T cell activity [ 25 ].…”

Section: Lymphomasmentioning

confidence: 99%

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Inflammasomes—New Contributors to Blood Diseases

Tomasik

Basak

2022

IJMS

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Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes’ contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives.

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Section: Discussionmentioning

confidence: 99%

Section: Lymphomasmentioning

confidence: 99%

Inflammasomes—New Contributors to Blood Diseases

Tomasik

Basak

2022

IJMS

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“…Leukocytes of peripheral blood or bone marrow were collected from the participants involved in our study. For the same patient, the DNA and RNA were extracted from the same type of biological sample 59–62 . Genomic DNA was isolated by standard methods according to the manufacturer's instruction of TIANamp blood DNA kit (Tiangen Biotech).…”

Section: Methodsmentioning

confidence: 99%

“…For the same patient, the DNA and RNA were extracted from the same type of biological sample. [59][60][61][62] Genomic DNA was isolated by standard methods according to the manufacturer's instruction of TIANamp blood DNA kit (Tiangen Biotech). The quality and concentration of DNA were determined using a DeNovix DS-11 Spectrophotometer (DeNovix Inc.).…”

Section: Dna Extractionmentioning

confidence: 99%

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

Can

Liu

et al. 2023

Cancer Medicine

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BackgroundThough immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear.MethodsWe investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune‐related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA.ResultsBy comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK–STAT, NF‐κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter‐OS genotypes.ConclusionsWe used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune‐related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

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“…Associations between polymorphisms and disease characteristics were also underscored. Namely, the TT genotype of CARD8 (rs2043211) was observed in patients with higher LDH levels, clinical stages III-IV, and international prognostic index (IPI) scores 3-5, although the relationship did not reach statistical significance [101]. Wang et al analyzed mutations and copy number variations (CNVs) of pyroptosis-related genes (PRGs) in DLBCL, unveiling multiple aberrations that also correlated with disease prognosis.…”

Section: The Effect Of Nlrp3 Inflammasome Activation In the B-cell Nh...mentioning

confidence: 99%

Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies

Stergiou,

Tsironis,

Papadakos

et al. 2024

IJMS

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Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome’s implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.

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Genetic Polymorphisms in NLRP3 Inflammasome-Associated Genes in Patients with B-Cell Non-Hodgkin’s Lymphoma

Cited by 6 publications

References 34 publications

Inflammasomes—New Contributors to Blood Diseases

Inflammasomes—New Contributors to Blood Diseases

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies

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