scholarly journals Identification of the 7-lncRNA Signature as a Prognostic Biomarker for Acute Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Chun-yu Liu ◽  
Hui-hui Guo ◽  
Hai-xia Li ◽  
Ying Liang ◽  
Cong Tang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cumulative Risk ◽  
Risk Scores ◽  
Sequencing Data ◽  
The Public ◽  
Target Database ◽  
Acute Myeloid

A lot of evidence has emphasized the function of long noncoding RNAs (lncRNAs) in tumors’ development and progression. Nevertheless, there is still a lack of lncRNA biomarkers that can predict the prognosis of acute myeloid leukemia (AML). Our goal was to develop a lncRNA marker with prognostic value for the survival of AML. AML patients’ RNA sequencing data as well as clinical characteristics were obtained from the public TARGET database. Then, differentially expressed lncRNAs were identified in female and male AML samples. By adopting univariate and multivariate Cox regression analyses, AML patients’ survival was predicted by a seven-lncRNA signature. It was found that 95 abnormal expressed lncRNAs existed in AML. Then, the analysis of multivariate Cox regression showed that, among them, 7 (LINC00461, RP11-309M23.1, AC016735.2, RP11-61I13.3, KIAA0087, RORB-AS1, and AC012354.6) had an obvious prognostic value, and according to their cumulative risk scores, these 7 lncRNA signatures could independently predict the AML patients’ overall survival. Overall, the prognosis of AML patients could be predicted by a reliable tool, that is, seven-lncRNA prognostic signature.

scholarly journals m6A-Related lncRNAs Affect Tumor Immune Microenvironment And Prognosis In Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Fangmin Zhong ◽  
Fangyi Yao ◽  
Ying Cheng ◽  
Jing Liu ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Risk Scores ◽  
In Vitro Assays ◽  
Immune Microenvironment ◽  
Cox Regression Analysis ◽  
Tumor Immune Microenvironment ◽  
The Relationship ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long-chain non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study, we identified m6A-related lncRNAs, and analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified SRSF10 as a regulator of TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.

scholarly journals Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Ding Li ◽  
Jiaming Liang ◽  
Cheng Cheng ◽  
Wenbin Guo ◽  
Shuolei Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Pearson Correlation ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Risk Scores ◽  
Hematopoietic Malignancy ◽  
Cox Regression Analysis ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with AML using the data downloaded from The Cancer Genome Atlas (TCGA) database.Methods: The RNA-seq and clinical data were obtained from the TCGA AML cohort. First, Pearson correlation analysis was performed to identify the m6A-related lncRNAs. Next, univariate Cox regression analysis was used to determine the candidate lncRNAs with prognostic value. Then, feature selection was carried out by Least absolute shrinkage and selection operator (LASSO) analysis, and seven eligible m6A-related lncRNAs were included to construct the prognostic risk signature. Kaplan–Meier and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive capacity of the risk signature both in the training and testing datasets. A nomogram was used to predict 1-year, 2-year, and 3-year overall survival (OS) of AML patients. Next, the expression levels of lncRNAs in the signature were validated in AML samples by qRT-PCR. Functional enrichment analyses were carried out to identify probable biological processes and cellular pathways. The ceRNA network was developed to explore the downstream targets and mechanisms of m6A-related lncRNAs in AML.Results: Seven m6A-related lncRNAs were identified as a prognostic signature. The low-risk group hold significantly prolonged OS. The nomogram showed excellent accuracy of the signature for predicting 1-year, 2-year and 3-year OS (AUC = 0.769, 0.820, and 0.800, respectively). Moreover, the risk scores were significantly correlated with enrichment in cancer hallmark- and malignancy-related pathways and immunotherapy response in AML patients.Conclusion: We developed and validated a novel risk signature with m6A-related lncRNAs which could predict prognosis accurately and reflect the immunotherapy response in AML patients.

scholarly journals A Simple-to-Use Nomogram for Predicting Survival in Children with Acute Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Feng Jiang ◽  
Xiang Yu ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Model ◽  
Cox Regression ◽  
Chromosomal Abnormalities ◽  
Web Based ◽  
Cox Regression Analysis ◽  
Predictive Variables ◽  
Target Database ◽  
Acute Myeloid

Background. The research analyzed a group of patients to develop a statistical nomogram and a web-based survival rate predictor for the comprehensive estimate of the overall survival (OS) of children with acute myeloid leukemia. Methods. Between 1999 to 2015, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to evaluate and randomly divide 440 children diagnosed with AML into the population of training ( n = 309 ) and validation ( n = 131 ). The analysis of Lasso Cox was used to identify separate predictive variables. We have used essential forecasting considerations to construct a nomogram and a web-based calculator focused on Cox regression analysis. Nomogram validation was tested through discrimination and calibration. Results. Compared to the multivariate training cohort models, a nomogram integrating gender, age of diagnose, WBC at diagnosis, bone marrow leukemic blast percentage, and chromosomal abnormalities [ t (8; 21), inv(16)] were designed for the prediction of OS. We also developed a predictive survival nomogram and a web-based calculator. C-indexes validated internally and checked externally were 0.747 and 0.716. The calibration curves have shown that the nomogram might accurately forecast 3-year and 5-year OS. Conclusions. A nomogram effectively predicts survival in children with AML. This prognostic model can be used in clinical practice.

scholarly journals Prognostic value of CIP2A gene expression in adult Egyptian acute myeloid leukemia patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Roxan E. Shafik ◽  
Azza M. Ibrahim ◽  
Fadwa Said ◽  
Naglaa M. Hassan ◽  
Hanan E. Shafik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Acute Myeloid

scholarly journals Pattern and prognostic value of FLT 3 ‐ ITD mutations in Chinese de novo adult acute myeloid leukemia

2018 ◽  
Vol 109 (12) ◽  
pp. 3981-3992
Author(s):  
Song‐Bai Liu ◽  
Qiao‐Cheng Qiu ◽  
Xie‐Bing Bao ◽  
Xiao Ma ◽  
Hong‐Zhi Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
De Novo ◽  
Acute Myeloid

The Prognostic Value of CXCR4 in Acute Myeloid Leukemia

2012 ◽  
pp. 1 ◽  
Author(s):  
Jeong Yeal Ahn ◽  
Katie Seo ◽  
Olga K. Weinberg ◽  
Daniel A. Arber
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Acute Myeloid

scholarly journals Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5824-5831 ◽  
Author(s):  
Ana Flávia Tibúrcio Ribeiro ◽  
Marta Pratcorona ◽  
Claudia Erpelinck-Verschueren ◽  
Veronika Rockova ◽  
Mathijs Sanders ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Gene Expression Signature ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
Or Gene ◽  
Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

scholarly journals An Immune Checkpoint-Related Gene Signature for Predicting Survival of Pediatric Acute Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Feng Jiang ◽  
Xin-Yu Wang ◽  
Ming-Yan Wang ◽  
Yan Mao ◽  
Xiao-Lin Miao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Immune Checkpoint ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Cox Regression ◽  
Secondary Data ◽  
Gene Signature ◽  
Pediatric Acute Myeloid Leukemia ◽  
Pediatric Aml ◽  
Acute Myeloid

Objective. The aim of this research was to create a new genetic signature of immune checkpoint-associated genes as a prognostic method for pediatric acute myeloid leukemia (AML). Methods. Transcriptome profiles and clinical follow-up details were obtained in Therapeutically Applicable Research to Generate Effective Treatments (TARGET), a database of pediatric tumors. Secondary data was collected from the Gene Expression Omnibus (GEO) to test the observations. In univariate Cox regression and multivariate Cox regression studies, the expression of immune checkpoint-related genes was studied. A three-mRNA signature was developed for predicting pediatric AML patient survival. Furthermore, the GEO cohort was used to confirm the reliability. A bioinformatics method was utilized to identify the diagnostic and prognostic value. Results. A three-gene (STAT1, BATF, EML4) signature was developed to identify patients into two danger categories depending on their OS. A multivariate regression study showed that the immune checkpoint-related signature (STAT1, BATF, EML4) was an independent indicator of pediatric AML. By immune cell subtypes analyses, the signature was correlated with multiple subtypes of immune cells. Conclusion. In summary, our three-gene signature can be a useful tool to predict the OS in AML patients.

Molecular annotation of extramedullary acute myeloid leukemia to identify prevalence of targetable mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7024-7024
Author(s):  
Somedeb Ball ◽  
Todd C Knepper ◽  
Yehuda Ethan Deutsch ◽  
Chirag K Bhagat ◽  
Justin M. Watts ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Cancer Center ◽  
Genomic Alteration ◽  
Risk Category ◽  
Molecular Architecture ◽  
Ngs Data ◽  
Acute Myeloid

7024 Background: Extramedullary (EM) involvement, including myeloid sarcoma (MS) and leukemia cutis (LC), is uncommon in patients with acute myeloid leukemia (AML). Mutational landscape of EM-AML is not well characterized, including concordance of sequencing data from EM vs. non-EM site (blood or bone marrow) and the potential for personalized targeted therapy in this patient cohort. Methods: In a multicenter retrospective study, clinical and genomic data were collected on EM-AML patients treated at Moffitt Cancer Center, Memorial Healthcare System, and University of Miami, as well as sequenced cases at a central laboratory. Next generation sequencing (NGS) data come from panels that interrogated 24- 406 genes, with 15 genes covered by all panels, including notably, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, and TP53. Survival estimates using Kaplan-Meier statistics and multivariate analysis with Cox-regression were performed in SPSS (v.26). Results: Our study included 58 patients with EM-AML. Median age at diagnosis was 62 years; 55% of patients were males. In our cohort, 34 (59%) patients had MS, and 19 (33%) had LC. EM-AML was noted during relapse in 60% of evaluable patients (n=45), and 31% had isolated EM disease. Patients with LC had a significantly worse median overall survival (OS) than those with MS (5.7 months vs. 21.9 months, p= 0.008); Pattern of EM involvement (MS vs. LC) remained an independent prognostic factor for OS (p= 0.04) in a multivariate analysis including disease setting (new diagnosis vs. relapse) and ELN risk category. Results of NGS performed during EM presentation were available in 48 patients, 19 of which had NGS data from EM site. Most commonly mutated genes were NRAS on EM site NGS (37%) and NPM1 on non-EM site NGS (28%). Based on EM NGS, 52% patients had a targetable genomic alteration, with 37% mutations in IDH, 21% NPM1, 5% FLT3, and 11% MLL-PTD. Five (two with concurrent M+EM disease) out of nine evaluable patients had significant discordance in targetable mutations between EM and non-EM NGS at EM-AML. Three of four patients who received treatment with IDH1/2 inhibitors based on EM NGS achieved complete response. Conclusions: EM-AML has a distinct molecular architecture with an inferior OS in LC vs. MS patients. We conclude that EM site NGS is critical in patients with EM-AML, as 52% have potentially targetable mutations and could benefit from specific targeted therapies.[Table: see text]

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