Document Type
Article
Publication Date
12-1-2016
Identifier
PMCID: PMC5497493 DOI: 10.1002/pbc.26157
Abstract
BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.
PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.
RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire study cohort. Increasing miR-155 expression was highly associated with the presence of FLT3/ITD mutations (P < 0.001) and high-risk disease (P < 0.001) and inversely associated with standard-risk (P = 0.008) and low-risk disease (P = 0.041). Patients with highest miR-155 expression had a complete remission (CR) rate of 46% compared with 82% in low expressers (P < 0.001) with a correspondingly lower event-free (EFS) and overall survival (OS) (P < 0.001 and P = 0.002, respectively). In a multivariate model that included molecular risk factors, high miR-155 expression remained a significant independent predictor of OS (P = 0.022) and EFS (0.019).
CONCLUSIONS: High miR-155 expression is an adverse prognostic factor in pediatric NK-AML patients. Specifically, high miR-155 expression not only correlates with FLT3/ITD mutation status and high-risk disease but it is also an independent predictor of worse EFS and OS.
Journal Title
Pediatric blood & cancer
Volume
63
Issue
12
First Page
2096
Last Page
2103
MeSH Keywords
Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; MicroRNAs; fms-Like Tyrosine Kinase 3
Keywords
AML; children; miR-155
Recommended Citation
Ramamurthy R, Hughes M, Morris V, et al. miR-155 expression and correlation with clinical outcome in pediatric AML: A report from Children's Oncology Group. Pediatr Blood Cancer. 2016;63(12):2096-2103. doi:10.1002/pbc.26157
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Hemic and Lymphatic Diseases Commons, Medical Genetics Commons, Neoplasms Commons, Oncology Commons, Pediatrics Commons
Comments
Grant support