As reported in the Journal of Clinical Oncology, Lim et al have identified a microRNA expression–based risk model associated with event-free survival in pediatric acute myeloid leukemia (AML). The study involved comprehensive miRNA sequencing of 1,362 pediatric AML samples, consisting of 1,303 primary, 22 refractory, and 37 relapse samples.
miRNA Risk Model
A total of 36 miRNAs were identified with expression levels at diagnosis that were highly associated with event-free survival. A novel miRNA-based risk classification scheme (AMLmiR36) was developed using the combined expression of these miRNAs. The risk classifier identifies patients at high risk (hazard ratio [HR] = 2.830, P ≤ .001) or low risk (HR = 0.323, P ≤ .001) of treatment failure independent of conventional karyotype or mutation status.
In validation studies, the AMLmiR36 model defined three distinct risk cohorts (P < .001) in a clinical trial population in which high-risk patients received hematopoietic stem cell transplantation instead of consolidation chemotherapy and identified a high-risk group (P < .001) in a clinical trial population from which patients with conventional high risk had been excluded.
With regard to miRNA-mRNA interactions, microRNA miR-106a-363 exhibited abundant expression in relapse and refractory samples; several candidate mRNA targets of miR-106a-5p were involved in oxidative phosphorylation, which is suppressed in treatment-resistant leukemic cells.
The investigators concluded: “To assess the utility of miRNAs for outcome prediction in patients with pediatric AML, we designed and validated a miRNA-based risk classification scheme. We also hypothesized that the abundant expression of miR-106a could increase treatment resistance via modulation of genes that are involved in oxidative phosphorylation.”
The study was supported by the National Cancer Institute, British Columbia Cancer Foundation, and St. Baldrick’s Foundation.
Marco A. Marra, PhD, FRSC, of the British Columbia Cancer Agency, is the corresponding author of the Journal of Clinical Oncology article.
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