S100A8 and S100A9 Promote Apoptosis of Chronic Eosinophilic Leukemia Cells

Lee, Ji-Sook; Lee, Na Rae; Kashif, Ayesha; Yang, Seung-Ju; Nam, Aryung; Song, Ik‐Chan; Gong, Soo Jung; Hong, Min; Kim, Geunyeong; Seok, Pu Reum; Lee, Myung‐Shin; Sung, Kee-Hyung; Kim, In Sik

doi:10.3389/fimmu.2020.01258

Cited by 24 publications

(23 citation statements)

References 40 publications

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“…BCG can stimulate TLR2/4 in bladder tumor cells to decrease cell proliferation and up-regulate apoptosis (Camargo et al, 2018). The activation of TLR4 can also induce apoptosis in multiple cancer types, such as leukemia, liver cancer, and colon cancer (Ren et al, 2018;Xiao et al, 2018;Lee et al, 2020). Cytotoxic effects and cytokine production of immune cells exert antitumor effects in the immune microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Xia

Sun

et al. 2021

Front. Cell Dev. Biol.

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BackgroundThe toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer.MethodsThe transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package “pRRophetic.” The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels.ResultsTLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-β pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer.ConclusionThis research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Xia

Sun

et al. 2021

Front. Cell Dev. Biol.

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“…In a similar way, it was shown that S100A8 and S100A9 both induce apoptosis of chronic eosinophilic leukemia (CEL) cells through impact on signaling and mRNA expression of FIP1L1-PDGFRa. Moreover, both S100A8 and A9 proteins could inhibit tumor progression of xenograft model of CEL [ 50 ].…”

Section: Pathogenic Role Of S100a8 and S100a9 In Acute Myeloid Andmentioning

confidence: 99%

Pathogenic Roles of S100A8 and S100A9 Proteins in Acute Myeloid and Lymphoid Leukemia: Clinical and Therapeutic Impacts

2021

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Deregulations of the expression of the S100A8 and S100A9 genes and/or proteins, as well as changes in their plasma levels or their levels of secretion in the bone marrow microenvironment, are frequently observed in acute myeloblastic leukemias (AML) and acute lymphoblastic leukemias (ALL). These deregulations impact the prognosis of patients through various mechanisms of cellular or extracellular regulation of the viability of leukemic cells. In particular, S100A8 and S100A9 in monomeric, homodimeric, or heterodimeric forms are able to modulate the survival and the sensitivity to chemotherapy of leukemic clones through their action on the regulation of intracellular calcium, on oxidative stress, on the activation of apoptosis, and thanks to their implications, on cell death regulation by autophagy and pyroptosis. Moreover, biologic effects of S100A8/9 via both TLR4 and RAGE on hematopoietic stem cells contribute to the selection and expansion of leukemic clones by excretion of proinflammatory cytokines and/or immune regulation. Hence, the therapeutic targeting of S100A8 and S100A9 appears to be a promising way to improve treatment efficiency in acute leukemias.

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“…É uma malignidade hematológica rara com níveis elevados de eosinófilos onde é caracterizada pela presença do gene de fusão FIP1L1-PDGFRA, as características diagnósticas incluem proliferação sustentada de precursores eosinofílicos com eosinofilia marcada no sangue periférico e medulo óssea (Lee et al, 2020;Morsia et al, 2020;Ruan et al, 2020).…”

Section: Leucemia Eosinofilica Crônica (Lec)unclassified

Manifestações orais nas doenças mieloproliferativas: Uma revisão de literatura

Nascimento¹,

Alves²,

Silva³

et al. 2021

RSD

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Objetivo: Abordar as manifestações causadas pelas alterações provenientes das diversas doenças mieloproliferativa na cavidade oral e as implicações na vida do paciente, de maneira a fornecer embasamento teórico que ajude no diagnóstico precoce e terapia dessas patologias. Materiais e Métodos: trata-se de uma revisão de literatura onde foi realizada uma busca nos bancos de dados relacionados às áreas da Saúde como: SCIELO, PUBMED e LILACS usando corte temporal de 2016 a 2020, com os descritores "hematologia" ou "doenças hematológicas"; "afecção" ou "manifestações orais" e "leucemia" ou "alterações hematologicas". Discussão: O presente trabalho está relacionado as alterações orais causadas pelas doenças mieloproliferativas, onde poucos são os relatos destas alterações na literatura, uma vez que não se tinha o conhecimento do acometimento da cavidade oral com as doenças, em busca de aprimorar o diagnostico diferencial este trabalho trás as principais alterações encontradas na literatura sobre as alterações bucais. Conclusão: Com isso é evidente a necessidade de acompanhamento multiprofissional dos pacientes acometidos por estas enfermidades e espera-se que esta pesquisa juntamente com pesquisas futuras, possa esclarecer as alterações provocadas pelas doenças mieloproliferativas, principalmente suas manifestações na cavidade oral, para um diagnostico diferencial e precoce. Dessa forma, concluímos que há uma relação direta das alterações clínicas na cavidade oral em indivíduos com doença mieloproliferativa.

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S100A8 and S100A9 Promote Apoptosis of Chronic Eosinophilic Leukemia Cells

Cited by 24 publications

References 40 publications

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis

Pathogenic Roles of S100A8 and S100A9 Proteins in Acute Myeloid and Lymphoid Leukemia: Clinical and Therapeutic Impacts

Manifestações orais nas doenças mieloproliferativas: Uma revisão de literatura

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