Targeting RIPK1 in AML cells carrying FLT3‐ITD

Hillert, Laura K.; Bettermann‐Bethge, Kira; Nimmagadda, Subbaiah Chary; Fischer, Thomas; Naumann, Michael; Lavrik, Inna N.

doi:10.1002/ijc.32246

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…CHIP/STUB1 regulated necroptosis through ubiquitination and lysosomal-dependent degradation of RIPK1 and RIPK3 ( Tang et al, 2018 ). In addition, RIPK1 in the myeloid progenitor with FLT3 mutations had a strongly increasing tendency ( Hillert et al, 2019 ). Furthermore, we established a nomogram model for predicting the OS of KIRC patients in combination with NRGscore and several clinicopathological characteristics.…”

Section: Discussionmentioning

confidence: 99%

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma

et al. 2022

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Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.

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Section: Discussionmentioning

confidence: 99%

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma

et al. 2022

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“…Abnormal gene expression is closely related to tumor prognosis. Studies have shown that NPM1 (9), FLT3 (10,11), C-KIT (12), AML1-ETO (13), RUNX1 (3,14), TP53 (3,15), CBFB/MYH11 (13,16), TET2 (17), DNMT3A (18), JAK-STAT (19), and CXCR4 (20,21) ,HOXA family (22), NAT10 (23) gene are associated with prognosis of AML. A few studies have shown altered DNA methylation in cancer, but the roles of key differentially methylated genes (DMGs) and differentially expressed genes (DEGs) in AML remain unclear.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-based prognostic biomarkers of acute myeloid leukemia patients

Gao

Shi

et al. 2019

Ann Transl Med

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Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disease that prevents normal myeloid differentiation with its common features. Its incidence increases with age and has a poor prognosis.Studies have shown that DNA methylation and abnormal gene expression are closely related to AML. Methods:The methylation array data and mRNA array data are from the Gene Expression Omnibus (GEO) database. Through the GEO data, we identified differential genes from tumors and normal samples. Then we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses on these differential genes. Protein-protein interaction (PPI) network construction and module analysis were performed to screen the highest-scoring modules. Next, we used SurvExpress software to analyze the genes in the highest-scoring module and selected potential prognostic genes by univariate and multivariate Cox analysis. Finally, the three genes screened by SurvExpress software were analyzed using the methylation analysis site MethSurv to explore AML associated methylation biomarkers. Results:We found three genes that can be used as independent prognostic factors for AML. These three genes are the low expression/methylation genes ATP11A and ITGAM, and the high expression/low methylation gene ZNRF2.Conclusions: In this study, we performed a comprehensive analysis of DNA methylation and gene expression to identify key epigenetic genes in AML.

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“…Wang et al demonstrated that the overexpression of lncRNA CASC7 increased the FASLG expression and promoted apoptosis of BC cells [36]. FLT3 is the most common mutation site in acute myeloid leukemia, and the mutation of FLT3 increased the expression level of RIPK1 and the sensitivities of necroptosis [37]. Recent studies indicated that zinc transporter SLC39A7 participated in regulating TNFR1-mediated necroptosis and activated endoplasmic reticulum stress in cells [38].…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients

Tan

et al. 2022

J Transl Med

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Necroptosis plays a major role in breast cancer (BC) progression and metastasis. Besides, necroptosis also regulates inflammatory response and tumor microenvironment. Here, we aim to explore the predictive signature based on necroptosis-related genes (NRGs) for predicting the prognosis and response to therapies. Using Lasso multivariate cox analysis, we firstly established the NRG signature based on TCGA database. A total of 6 NRGs (FASLG, IPMK, FLT3, SLC39A7, HSP90AA1, and LEF1), which were associated with the prognosis of BC patients, were selected to establish our signature. Next, CIBERSORT algorithm was utilized to evaluate immune cell infiltration levels. We compare the response to immunotherapy using IMvigor 210 database, and also compared immune indicators in two risk groups via multiple methods. The biological function of IPMK was explored via in vitro verification. Finally, our results indicated that the signature was an independent prognostic indicator for BC patients with better efficiency than other reported signatures. The immune cell infiltration levels were higher, and the response to immunotherapy and chemotherapy was better in the low-risk groups. Besides, other immunotherapy-related factors, including TMB, TIDE, and expression of immune checkpoints were also increased in the low-risk group. Clinical sample validation showed that CD206 and IPMK in clinical samples were both up-regulated in the high-risk group. In vitro assay showed that IPMK promoted BC cell proliferation and migration, and also enhanced macrophage infiltration and M2 polarization. In summary, we successfully established the NRG signature, which could be used to evaluate BC prognosis and identify patients who will benefit from immunotherapy.

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Targeting RIPK1 in AML cells carrying FLT3‐ITD

Cited by 15 publications

References 49 publications

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma

DNA methylation-based prognostic biomarkers of acute myeloid leukemia patients

Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients

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