ArticleCancer2017
Prognostic methylation markers for overall survival in cytogenetically normal patients with acute myeloid leukemia treated on SWOG trials.
Article in Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- A novel 5-gene prognostic signature to improve risk stratification of cytogenetically normal acute myeloid leukemia.Journal of cancer research and clinical oncology · 2023Article
- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
- Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Bioinformatics and the Role of NR6A1 in the Progression of HCC.Journal of clinical and translational hepatology · 2022Article
- Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia.Blood advances · 2022Article
- A validation study of potential prognostic DNA methylation biomarkers in patients with acute myeloid leukemia using a custom DNA methylation sequencing panel.Clinical epigenetics · 2022Article
- Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia.Annals of translational medicine · 2020Article
- Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Article
- LZTS2 promoter hypermethylation: a potential biomarker for the diagnosis and prognosis of laryngeal squamous cell carcinoma.World journal of surgical oncology · 2018Article
- Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report.Biopreservation and biobanking · 2018Article
- MicroRNA-181 as a prognostic biomarker for survival in acute myeloid leukemia: a meta-analysis.Oncotarget · 2017Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundAberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML-NK).
methodsAML-NK samples from 7 SWOG trials were analyzed using a novel genome-wide approach called "CHARMcox" (comprehensive high-throughput array-based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates. CHARMcox was applied to a phase 1 discovery cohort (72 patients) to identify survival-associated methylation regions (SAMRs). Subsequently, using bisulfite pyrosequencing, SAMRs were studied in phase 2 model-building (65 patients) and phase 3 validation (65 patients) cohorts. An independent external cohort from The Cancer Genome Atlas (TCGA) AML study (LAML) was used for further validation (93 patients).
resultsTwo SAMRs, located at the CpG island shores of leucine zipper tumor suppressor 2 (LZTS2) and nuclear receptor subfamily 6 group a member 1 (NR6A1), respectively, were identified. Multivariable analyses demonstrated that hypomethylation of either LZTS2 or NR6A1 was associated with worse overall survival in the SWOG cohort (P<.001). The prognosis was validated in patients with AML-NK from the TCGA-LAML cohort. Methylation values below the median at both markers predicted worse overall survival (SWOG: hazard ratio, 1.89 [P<.001]; and TCGA-LAML: hazard ratio, 2.08 [P=.006]). The C-statistic was 0.71 for both cohorts, and the impact was independent of the Fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD) status.
conclusionsThe 2 methylation markers, measurable by clinically applicable assays such as bisulfite pyrosequencing, are promising for risk stratification among patients with AML-NK. Cancer 2017;123:2472-81. © 2017 American Cancer Society.
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