Toll-like receptor 9 negatively related to clinical outcome of AML patients

Al-Kahiry, Waiel; Dammag, Enas A; Abdelsalam, Hadeel Said Tawfik; Fadlallah, Hayat K.; Owais, Mona S.

doi:10.1186/s43046-020-00027-3

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…The present study showed that variant genotypes of the TLR2 rs5743708, TLR4 (rs11536889, rs4986790), and TLR9 (rs187084, rs352140, rs5743836) gene polymorphisms were not associated with AML risk. Our findings are partly similar to those reported by other studies previously [ 14 ]. Thus, no significant difference between cancers and controls for TLR2 rs5743708 SNP was reported in a meta-analysis conducted by Wang et al [ 32 ].…”

Section: Discussionsupporting

confidence: 94%

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Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

Bănescu

Tripon

Bojan

et al. 2022

JPM

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Toll-like receptors (TLRs) have an important role in innate immunity, and single nucleotide polymorphisms (SNPs) of TLR genes influence the risk of developing hematological malignancies. We aimed to evaluate the effect of TLR2 (rs5743708), TLR4 (rs11536889, rs4986790, rs4986791), TLR9 (rs187084, rs352140, rs5743836) on AML risk, the relation between investigated SNPs and somatic mutations, clinical features, and the overall survival of adult AML patients. All mentioned SNPs were genotyped in 511 AML cases and 503 healthy controls. DNMT3A (R882), FLT3 (D835, ITD), and NPM1 mutations’ status were investigated in AML patients. TLR4 rs4986791 was associated with an increased risk of AML under the dominant model (OR = 1.61, 95% CI: 1.001–2.59). Variant genotypes of the TLR4 rs4986790 or rs4986791 were associated with the odds of developing AML in the codominant model (OR = 3.14; 95% CI: 1.12–8.84; p = 0.032). The TLR9 rs5743836 variant genotype was associated with the NPM1 mutation (p = 0.002). The investigated SNPs were not associated with the DNMT3A, FLT3 mutations and had no significant contribution to the hazard of death after adjusting for covariates. Our findings suggest that TLR4 rs4986791 is associated with AML susceptibility. The combined variant genotypes of TLR4 rs4986790 and rs4986791 increase AML risk, the TLR9 C-G-A haplotype may represent a promising approach to predict a person’s risk for developing AML.

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Section: Discussionsupporting

confidence: 94%

“…TLRs play an important role in triggering both the immune response and the inflammatory process. In different cancers, an altered expression of TLR genes had been reported [ 14 ]. Altered TLR signaling was linked to hematopoietic dysfunction and malignancy.…”

Section: Introductionmentioning

confidence: 99%

Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

Bănescu

Tripon

Bojan

et al. 2022

JPM

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“…These ndings suggest that LST1 overexpression may rewire the signaling network in AML cells, leading to heightened in ammatory responses and immune evasion. Importantly, previous studies have documented the activation of chemokine and Toll-like receptor signaling in AML, promoting leukemia cell proliferation, migration, and survival [31][32][33]. The outcomes of our research offer a new understanding of the molecular pathways implicated in the impact of increased LST1 levels on the progression of AML.…”

Section: Discussionmentioning

confidence: 68%

LST1 Expression Correlates with Immune Infiltration and Predicts Poor Prognosis in Acute Myeloid Leukemia

Xu,

Chen,

Zhong

et al. 2024

Preprint

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Clinical management of acute myeloid leukemia (AML) poses significant challenges due to its poor prognosis and heterogeneous nature. Discovering new biomarkers is crucial for improving risk assessment and customizing treatment approaches. While leukocyte-specific transcript 1 (LST1) is implicated in inflammation and immune regulation, its function in AML remains ambiguous. In this investigation, we conduct a comprehensive investigation into LST1 expression profiles, clinical implications, functional pathways, and immune interactions in AML, leveraging multi-omics data and experimental validations. Our examination shows increased levels of LST1 expression in AML when compared to regular hematopoietic tissues, a discovery validated by RT-qPCR and Western blot analyses in a separate group. Elevated LST1 levels correlate with distinct clinicopathological features, including increased white blood cell counts, non-M3 FAB subtype, and intermediate/poor cytogenetic risk. Importantly, heightened LST1 levels predict unfavorable overall survival outcomes across various subgroups, independently of age and cytogenetic risk. We develop an integrative nomogram incorporating LST1 expression, demonstrating robust prognostic efficacy for patient survival. Transcriptomic profiling identifies 275 differentially expressed genes between LST1-high and -low AML cases, enriched in cytokine signaling, immune modulation, cell adhesion, and oncogenic pathways. Furthermore, LST1 exhibits significant associations with the infiltration of diverse immune cell subsets within the AML microenvironment, particularly myeloid cells and regulatory T cells (Tregs). In conclusion, our study establishes LST1 as a novel prognostic indicator with immunological relevance in AML, emphasizing its potential therapeutic implications. Further mechanistic elucidation of LST1 in AML pathogenesis is crucial for its clinical translation.

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“…TLR-9 expression in leukemic cells of AML patients with a very low percentage compared to healthy control according to previous a previous study in a neighboring country (Egypt) that contradicted the result of the current study. The expression of TLR-9 was negatively related to the clinical outcome 31 . Cytokines affect the growth of all types of cells in the blood and body cells, which in turn help stimulate the immune response and inflammation 32 .…”

Section: A-roc Curve Of Tlr-9 B-roc Curve Of Tnfα and C-roc Curve Of ...mentioning

confidence: 95%

Estimation of Serum TLR-9,TNF-α, and IL-6 Levels in the Iraqi Patients Diagnosed as Acute Myelogenous Leukemia

Mohammed,

Alwan,

Almukhtar

2024

Baghdad Sci.J

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Acute myelogenous leukemia (AML) is a varied group of biological and clinical diseases. It is distinguished by the fast proliferation of aberrant cells in the bone marrow, which interferes with normal blood cell formation. Several studies demonstrated that cytokines released by leukemic cells in an autocrine or paracrine manner influence the proliferation of AML cells. Our study aimed to assess serum levels of TLR-9, TNF-α and, IL-6 in patients of AML. The study was done via the ELISA Technique. The results show a highly significant difference in all parameters in Patients and control. The correlation between immunological parameters using the Pearson correlation coefficient for patients showed that there is a weak correlation between TLR-9 and TNF- α, IL-6 with P-values of 0.47 and 0.23 respectively. This may indicate the complex environment of inflammation. However, there was a strong correlation between TNF- α and IL-6 with a P-value (0.001). This indicates that the secretion of these cytokines was high in patients. All immunological parameters of patients were evaluated using the receiver operating characteristic (ROC) curve to demonstrate that any one of them is a useful tool for identifying and tracking inflammation. The ROC curve's findings revealed that all parameters have good sensitivity and specificity for detecting inflammation and disease activity in AML patients. According to the current study, AML was related to higher levels of TLR-9, TNF-α, and, IL-6 may be affected the prognosis of the disease, increase the risk of the disease progression, and may be used as a biomarker to target AML cells.

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Toll-like receptor 9 negatively related to clinical outcome of AML patients

Cited by 6 publications

References 22 publications

Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

LST1 Expression Correlates with Immune Infiltration and Predicts Poor Prognosis in Acute Myeloid Leukemia

Estimation of Serum TLR-9,TNF-α, and IL-6 Levels in the Iraqi Patients Diagnosed as Acute Myelogenous Leukemia

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