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Development and Validation of a Novel RNA Sequencing–Based Prognostic Score for Acute Myeloid Leukemia

BACKGROUND: Recent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML). METHODS: We compared the prognostic value of traditional demographic and cytogene...

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Detalles Bibliográficos
Autores principales: Wang, Mei, Lindberg, Johan, Klevebring, Daniel, Nilsson, Christer, Lehmann, Sören, Grönberg, Henrik, Rantalainen, Mattias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186516/
https://www.ncbi.nlm.nih.gov/pubmed/29506270
http://dx.doi.org/10.1093/jnci/djy021
Descripción
Sumario:BACKGROUND: Recent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML). METHODS: We compared the prognostic value of traditional demographic and cytogenetic risk factors, genomic data in the form of somatic aberrations of 25 AML-relevant genes, and whole-transcriptome expression profiling (RNA sequencing) in 267 intensively treated AML patients (Clinseq-AML). Multivariable penalized Cox models (overall survival [OS]) were developed for each data modality (clinical, genomic, transcriptomic), together with an associated prognostic risk score. RESULTS: Of the three data modalities, transcriptomic data provided the best prognostic value, with an integrated area under the curve (iAUC) of a time-dependent receiver operating characteristic (ROC) curve of 0.73. We developed a prognostic risk score (Clinseq-G) from transcriptomic data, which was validated in the independent The Cancer Genome Atlas AML cohort (RNA sequencing, n = 142, iAUC = 0.73, comparing the high-risk group with the low-risk group, hazard ratio [HR](OS) = 2.42, 95% confidence interval [CI] = 1.51 to 3.88). Comparison between Clinseq-G and ELN score iAUC estimates indicated strong evidence in favor of the Clinseq-G model (Bayes factor = 26.78). The proposed model remained statistically significant in multivariable analysis including the ELN and other well-known risk factors (HR(os) = 2.34, 95% CI = 1.30 to 4.22). We further validated the Clinseq-G model in a second independent data set (n = 458, iAUC = 0.66, adjusted HR(OS) = 2.02, 95% CI = 1.33 to 3.08; adjusted HR(EFS) = 2.10, 95% CI = 1.42 to 3.12). CONCLUSIONS: Our results indicate that the Clinseq-G prediction model, based on transcriptomic data from RNA sequencing, outperforms traditional clinical parameters and previously reported models based on genomic biomarkers.