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High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

ABSTRACT: Background:Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML. Methods:To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens. Results:In the chemotherapy group, cases with upregulated miR-25 expression showed relatively longer overall survival (OS; P?=?0.0086) and event-free survival (EFS; P?=?0.019). Multivariable analyses revealed that miR-25 upregulation is an independent predictor for extended OS (HR?=?0.556, P?=?0.015) and EFS (HR?=?0.598, P?=?0.03). In addition, allogeneic hematopoietic stem cell transplantation (allo-HSCT) circumvented the poor prognosis that was related to miR-25 downregulation with chemotherapy. The expression level pattern of miR-25 coincided with AML differentiation and proliferation, which included HOXA and HOXB cluster members, as well as the HOX cofactor MEIS1. The MYH9 gene was identified as a direct target of miR-25. Conclusions:The miR-25 levels are correlated with prognosis in AML independently of other powerful molecular markers. The expression of miR-25 may contribute to the selection of the optimal treatment regimen between chemotherapy and allo-HCST for AML patients.

SUBMITTER: Niu M

PROVIDER: S-EPMC6505210 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

Niu Mingshan M Feng Yuan Y Zhang Ninghan N Shao Tingting T Zhang Huihui H Wang Rong R Yao Yao Y Yao Ruosi R Wu Qingyun Q Cao Jiang J Liu Xuejiao X Liu Yubo Y Xu Kailin K

Cancer cell international 20190507

<h4>Background</h4>Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML.<h4>Methods</h4>To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens.<h4>Results</h4>In the chemotherapy group, cases with upregulated miR-25 expression sh ...[more]

PMID: 31080363

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Project description:PurposeOptimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML.MethodsTo identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis.ResultsTraining set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays.ConclusionInclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.

Dataset Information

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

Publications

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

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