Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation

Saadi, Mahdiyar Iravani; Ramzi, Mani; Hosseinzadeh, Mehran; Ebrahimi, Narjes; Owjfard, Maryam; Abdolyousefi, Ehsan Nabi; Hesami, Zahra; Valibeigi, Behnaz; Zareei, Neda; Tavasolian, Fataneh; Haghighinejad, Hourvash; Zare, Abdolhossein

doi:10.1007/s13193-021-01358-w

Cited by 7 publications

(8 citation statements)

References 42 publications

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“…In AML patients with reduced OS, blood and BM serum levels of IL-6 are increased (39,53,131). Further studies confirm these findings and suggest that IL-6 levels correlate with poor prognosis, rapid disease progression, and resistance to chemotherapy (39,(132)(133)(134). The combined assessment of PB IL-6 and FLT3-ligand levels during AML induction therapy revealed that patients with persistent high IL-6 levels display lower survival rates compared to patients with decreasing IL-6 and increasing FLT3-ligand levels (134).…”

Section: Interleukin-6mentioning

confidence: 79%

The cytokine network in acute myeloid leukemia

2022

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Acute myeloid leukemia (AML) is a highly heterogeneous malignancy of the blood and bone marrow, characterized by clonal expansion of myeloid stem and progenitor cells and rapid disease progression. Chemotherapy has been the first-line treatment for AML for more than 30 years. Application of recent high-throughput next-generation sequencing technologies has revealed significant molecular heterogeneity to AML, which in turn has motivated efforts to develop new, targeted therapies. However, due to the high complexity of this disease, including multiple driver mutations and the coexistence of multiple competing tumorigenic clones, the successful incorporation of these new agents into clinical practice remains challenging. These continuing difficulties call for the identification of innovative therapeutic approaches that are effective for a larger cohort of AML patients. Recent studies suggest that chronic immune stimulation and aberrant cytokine signaling act as triggers for AML initiation and progression, facets of the disease which might be exploited as promising targets in AML treatment. However, despite the greater appreciation of cytokine profiles in AML, the exact functions of cytokines in AML pathogenesis are not fully understood. Therefore, unravelling the molecular basis of the complex cytokine networks in AML is a prerequisite to develop new therapeutic alternatives based on targeting cytokines and their receptors.

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Section: Interleukin-6mentioning

confidence: 79%

The cytokine network in acute myeloid leukemia

2022

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“…Saadi et al [ 19 ] evaluated the expression levels of IL18 in AML patients according to their response to treatment and showed that expression levels of IL18 were increased in AML patients who did not respond to therapy compared to those patients who respond to therapy. Furthermore, it was observed that the expression levels of IL18 were significantly increased in high-risk groups of AML patients [ 19 ]. A correlation was observed between the levels of IL18 and the prognosis of AML, i.e., higher levels of IL18 were correlated with worse prognosis of AML [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…A correlation was observed between the levels of IL18 and the prognosis of AML, i.e., higher levels of IL18 were correlated with worse prognosis of AML [ 20 ]. The expression profiles of IL-6 and IL18 were considered as prognostic markers for AML [ 19 ]. Furthermore, the higher expression levels of IL18 and its receptor induced drug resistance in AML [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Gene Regulatory Network Analysis between Azacitidine-Sensitive and -Resistant Cell Lines

Park,

Miyano

2024

IJMS

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Azacitidine, a DNA methylation inhibitor, is employed for the treatment of acute myeloid leukemia (AML). However, drug resistance remains a major challenge for effective azacitidine chemotherapy, though several studies have attempted to uncover the mechanisms of azacitidine resistance. With the aim to identify the mechanisms underlying acquired azacitidine resistance in cancer cell lines, we developed a computational strategy that can identify differentially regulated gene networks between drug-sensitive and -resistant cell lines by extending the existing method, differentially coexpressed gene sets (DiffCoEx). The technique specifically focuses on cell line-specific gene network analysis. We applied our method to gene networks specific to azacitidine sensitivity and identified differentially regulated gene networks between azacitidine-sensitive and -resistant cell lines. The molecular interplay between the metallothionein gene family, C19orf33, ELF3, GRB7, IL18, NRN1, and RBM47 were identified as differentially regulated gene network in drug resistant cell lines. The biological mechanisms associated with azacitidine and AML for the markers in the identified networks were verified through the literature. Our results suggest that controlling the identified genes (e.g., the metallothionein gene family) and “cellular response”-related pathways (“cellular response to zinc ion”, “cellular response to copper ion”, and “cellular response to cadmium ion”, where the enriched functional-related genes are MT2A, MT1F, MT1G, and MT1E) may provide crucial clues to address azacitidine resistance in patients with AML. We expect that our strategy will be a useful tool to uncover patient-specific molecular interplay that provides crucial clues for precision medicine in not only gastric cancer but also complex diseases.

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“…However, observational studies on the association between circulating IL-18 levels and AML are limited to date. A case-control study involving 70 patients and 50 controls reported that there were no differences in the expression level of IL-18 in patients with AML compared to healthy controls ( P =0.100) ( 32 ), while another study of 47 patients with AML found that IL-18 was associated with unfavorable prognostic factors of AML ( 33 ). The potential mechanism may be that IL-18 plays an important role in anti-tumor immunity through enhancing interferon-γ production and Fas ligand dependent cytotoxicity of immune cells, and the dose of IL-18 was correlated with the level of serum IFN-γ.…”

Section: Discussionmentioning

confidence: 99%

Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer

Song

et al. 2022

Front. Immunol.

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BackgroundInflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach.MethodWe used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test.Results224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance (P<5×10-8) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69, P=5.39×10-7), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36, P=1.25×10-5) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10-5≤P<0.05).ConclusionsBy using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation.

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Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation

Cited by 7 publications

References 42 publications

The cytokine network in acute myeloid leukemia

The cytokine network in acute myeloid leukemia

Differential Gene Regulatory Network Analysis between Azacitidine-Sensitive and -Resistant Cell Lines

Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer

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