Browse
Submit Data
Databases
API
Help

Dataset Information

34 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Prognostic Prediction of Cytogenetically Normal Acute Myeloid Leukemia Based on a Gene Expression Model.

ABSTRACT: Acute myeloid leukemia (AML) refers to a heterogeneous group of hematopoietic malignancies. The well-known European Leukemia Network (ELN) stratifies AML patients into three risk groups, based primarily on the detection of cytogenetic abnormalities. However, the prognosis of cytogenetically normal AML (CN-AML), which is the largest AML subset, can be hard to define. Moreover, the clinical outcomes associated with this subgroup are diverse. In this study, using transcriptome profiles collected from CN-AML patients in the BeatAML cohort, we constructed a robust prognostic Cox model named NEST (Nine-gEne SignaTure). The validity of NEST was confirmed in four external independent cohorts. Moreover, the risk score predicted by the NEST model remained an independent prognostic factor in multivariate analyses. Further analysis revealed that the NEST model was suitable for bone marrow mononuclear cell (BMMC) samples but not peripheral blood mononuclear cell (PBMC) samples, which indirectly indicated subtle differences between BMMCs and PBMCs. Our data demonstrated the robustness and accuracy of the NEST model and implied the importance of the immune dysfunction in the leukemogenesis that occurs in CN-AML, which shed new light on the further exploration of molecular mechanisms and treatment guidance for CN-AML.

SUBMITTER: Yang L

PROVIDER: S-EPMC8190396 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Molecular prognostic factors in cytogenetically normal acute myeloid leukemia.

Project description:Chromosomal abnormalities are detected in 50-60% of patients with acute myeloid leukemia (AML) and are important predictors of prognosis and risk of relapse. The remaining patients, those with cytogenetically normal AML, are a seemingly homogeneous group that in fact consists of subsets of patients with distinct clinical outcomes. This heterogeneity is likely related to acquired gene mutations, as well as altered miRNA and gene-expression profiles, which occur within the group. The identification of recurrent molecular abnormalities has improved prognostication and provided insight into mechanisms of leukemogenesis for patients with cytogenetically normal AML, as well as led to the discovery of novel therapeutic targets. As the number of mutations continues to expand, bioinformatic algorithms that allow for integration of multiple markers will be necessary to provide optimal care for patients with this disease.

| S-EPMC3582378 | biostudies-literature

A 6-Membrane Protein Gene score for prognostic prediction of cytogenetically normal acute myeloid leukemia in multiple cohorts.

Project description:Background: Cytogenetically normal acute myeloid leukemia (CN-AML) is a large proportion of AMLs with diverse prognostic outcomes. Identifying membrane protein genes as prognostic factors to stratify CN-AML patients will be critical to improve their outcomes. Purpose: This study aims to identify prognostic factors to stratify CN-AML patients to choose better treatments and improve their outcomes. Methods: CN-AML data were from TCGA cohort (n = 79) and four GEO datasets. We identified independent prognostic genes by Cox regression and Kaplan-Meier methods, and constructed linear regression model using LASSO algorithm. The prediction error curve was calculated using R package "pec". Results: Based on independent prognostic membrane genes, we constructed a regression model for CN-AML prognosis prediction: score = (0.0492 * CD52) - (0.0018 * CD96) + (0.0131 * EMP1) + (0.2058 * TSPAN2) + (0.0234 * STAB1) - (0.3658 * MBTPS1), which was named as MPG6 (6-Membrane Protein Gene) score. Tested in multiple CN-AML datasets, consistent results showed that CN-AML patients with high MPG6 score had poor survival, higher WBC count and shorter EFS. Comparing with other reported scoring models, the benchmark result of MPG6 achieved better association with survival in multiple cohorts. Moreover, by combining with other clinical indicators in CN-AML, MPG6 could improve the performance of survival prediction and serve as a robust prognostic factor. Conclusions: We identified the MPG6 score as a stable indicator with great potential for clinical application in risk stratification and outcome prediction in CN-AML.

| S-EPMC6930412 | biostudies-literature

The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia.

Project description:Acute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.

| S-EPMC6861270 | biostudies-literature

Development of gene expression-based risk score in cytogenetically normal acute myeloid leukemia patients.

Project description:Patients with normal karyotype represent the single largest cytogenetic group of acute myeloid leukemia (AML), with highly heterogeneous clinical and molecular characteristics. In this study, we sought to determine new prognostic biomarkers in cytogenetically normal (CN)-AML patients. A gene expression (GE)-based risk score was built, summing up the prognostic value of 22 genes whose expression is associated with a bad prognosis in a training cohort of 163 patients. GE-based risk score allowed identifying a high-risk group of patients (53.4%) in two independent cohorts of CN-AML patients. GE-based risk score and EVI1 gene expression remained independent prognostic factors using multivariate Cox analyses. Combining GE-based risk score with EVI1 gene expression allowed the identification of three clinically different groups of patients in two independent cohorts of CN-AML patients. Thus, GE-based risk score is powerful to predict clinical outcome for CN-AML patients and may provide potential therapeutic advances.

| S-EPMC3478459 | biostudies-literature

Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia.

Project description:Although ∼80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half of them relapse. Better identification of patients who are likely to relapse can help to inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML who were younger than 60 years of age and achieved a CR after induction treatment with standard "7+3" chemotherapy. After filtering for genes whose expressions were associated with gene mutations known to impact outcome (ie, CEBPA, NPM1, and FLT3-internal tandem duplication [FLT3-ITD]), we identified a 10-gene signature that was strongly predictive of patient relapse (area under the receiver operating characteristics curve [AUC], 0.81). The signature consisted of 7 coding genes (GAS6, PSD3, PLCB4, DEXI, JMY, NRP1, C10orf55) and 3 long noncoding RNAs. In multivariable analysis, the 10-gene signature was strongly associated with relapse (P < .001), after adjustment for the FLT3-ITD, CEBPA, and NPM1 mutational status. Validation of the expression signature in an independent patient set from The Cancer Genome Atlas showed the signature's strong predictive value, with AUC = 0.78. Implementation of the 10-gene signature into clinical prognostic stratification could be useful for identifying patients who are likely to relapse.

| S-EPMC7948288 | biostudies-literature

An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.

Project description:Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML.

| S-EPMC2954679 | biostudies-literature

Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia.

Project description:DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (?60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall (OS; P<0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P=0.04) and shorter DFS (P=0.04) and OS (P=0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients.

| S-EPMC4351165 | biostudies-literature

Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia.

Project description:PURPOSE:Uniparental disomy (UPD) is a way cancer cells duplicate a mutated gene, causing loss of heterozygosity (LOH). Patients with cytogenetically normal acute myeloid leukemia (CN-AML) do not have microscopically detectable chromosome abnormalities, but can harbor UPDs. We examined the prognostic significance of UPDs and frequency of LOH in patients with CN-AML.Experimental Design: We examined the frequency and prognostic significance of UPDs in a set of 425 adult patients with de novo CN-AML who were previously sequenced for 81 genes typically mutated in cancer. Associations of UPDs with outcome were analyzed in the 315 patients with CN-AML younger than 60 years. RESULTS:We detected 127 UPDs in 109 patients. Most UPDs were large and typically encompassed all or most of the affected chromosome arm. The most common UPDs occurred on chromosome arms 13q (7.5% of patients), 6p (2.8%), and 11p (2.8%). Many UPDs significantly cooccurred with mutations in genes they encompassed, including 13q UPD with FLT3-internal tandem duplication (FLT3-ITD; P < 0.001), and 11p UPD with WT1 mutations (P = 0.02). Among patients younger than 60 years, UPD of 11p was associated with longer overall survival (OS) and 13q UPD with shorter disease-free survival (DFS) and OS. In multivariable models that accounted for known prognostic markers, including FLT3-ITD and WT1 mutations, UPD of 13q maintained association with shorter DFS, and UPD of 11p maintained association with longer OS. CONCLUSIONS:LOH mediated by UPD is a recurrent feature of CN-AML. Detection of UPDs of 13q and 11p might be useful for genetic risk stratification of patients with CN-AML.

| S-EPMC6825549 | biostudies-literature

Phe354Leu Polymorphism of LKB1 Is a Potential Prognostic Factor for Cytogenetically Normal Acute Myeloid Leukemia.

Project description:BACKGROUND/AIM:Liver kinase B1 (LKB1) is a major activator of the AMP-dependent kinase/mammalian target of rapamycin pathway. The prevalence and the specificity of LKB1 gene mutation in acute myeloid leukemia (AML) have not been well established. This study aimed to examine mutation of LKB1 in AML and its clinical and pathological implications. PATIENTS AND METHODS:Eighty-five patients newly diagnosed with cytogenetically normal AML were analyzed using polymerase chain reaction followed by direct sequencing. RESULTS:A silent mutation (837C>T) of LKB1 was detected in one patient and a pathogenic polymorphism Phe354Leu which diminishes LKB1 ability to maintain cell polarity was detected in six (7%) patients. The Phe354Leu polymorphism occurred concurrently with mutations of nucleophosmin 1 (NPM1), fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer binding protein alpha (CEBPA), but not with metabolism-related genes, isocitrate dehydrogenase [nicotinamide adenine dinucleotide phosphate (+)]1 (IDH1) and IDH2. Patients with Phe354Leu polymorphism diagnosed at younger ages had a worse overall survival. CONCLUSION:LKB1 may be involved in the leukemogenesis and progression of cytogenetically normal AML.

| S-EPMC5656856 | biostudies-literature

Prognostically important molecular markers in cytogenetically normal acute myeloid leukemia.

Project description:Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with variable clinical outcomes. Emerging data has identified molecular markers that provide additional prognostic information to better classify these patients into those with a more favorable prognosis and those with an unfavorable prognosis who may require more aggressive or investigational therapies. Markers such as mutations in nucleophosmin 1 gene and CCAAT/enhancer binding protein alpha gene have been associated with a more favorable prognosis in CN-AML. In contrast, FMS-related tyrosine kinase 3 mutations, partial tandem duplication of mixed-lineage leukemia gene and overexpression of brain and acute leukemia, cytoplasmic gene are associated with inferior clinical outcomes. In this article, the authors discuss the classical clinical features of AML and the importance of cytogenetics that predict prognosis in AML. They review the best-described molecular markers in CN-AML and their significance to clinical decision making in CN-AML.

| S-EPMC4234091 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data