Publication Date:
2019-11-13
Description:
Background: Aberrant expression levels of several miRs have been reported to independently associate with outcome of patients (pts) with CN-AML. In these reports, miR expression was profiled using microarray assays, which interrogate a selected subset of miRs. The advent of next-generation sequencing (NGS) has allowed unbiased measurement of miR expression, but, to our knowledge, NGS has not been used to identify miRs associated with prognosis of AML pts. Here, we analyze small RNA sequencing (smRNA-seq) data from a large cohort of younger adults with CN-AML, for whom outcome data were available, with the goal to identify new prognostic miRs. Methods: We performed smRNA-seq in 281 younger adults (aged 18-59 y) with de novo CN-AML. Cytogenetic analyses were performed in Cancer and Leukemia Group B (CALGB)/Alliance institutional laboratories using standard banding techniques; mutational analyses were done centrally using a targeted DNA sequencing platform. All pts were treated on frontline CALGB/Alliance protocols. Results: We first evaluated which miRs associated with overall survival (OS) in univariable analysis; we detected 9 such miRs. We then used a machine-learning approach, namely random forests, to identify miRs whose concomitant expression could generate an effective outcome predictor in CN-AML. To account for the effect of co-existing prognostic gene mutations, we included the European LeukemiaNet (ELN) risk group status in the random forest analyses. A total of 8 prognostic miRs were identified, 4 of which were also found to be prognostic in univariable analysis (underlined below), thus bringing the total number of unique prognostic miRs to 13: miR-511, miR-1193, miR-155, miR-4517, miR-3681, miR-2355, miR-628, miR-1266, miR-6715a, miR-1180, miR-6715b, miR-132, miR-146b. We used partitioning around medoids to divide our pts into clusters, based on the combined expression levels of the 13 prognostic miRs. Two such clusters were identified: cluster 1 comprised 173 pts and cluster 2 contained 108 pts. Regarding pretreatment and molecular features, pts in cluster 1 had lower percent of bone marrow blasts (P=.04), and had more frequently biallelic CEBPA mutations (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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