Small RNA sequencing profiles of mir-181 and mir-221, the most relevant microRNAs in acute myeloid leukemia.

Background/Aims: To evaluate and select microRNAs relevant to acute myeloid leukemia (AML) pathogenesis, we analyzed differential microRNA expression by quantitative small RNA next-generation sequencing using duplicate marrow samples from individual AML patients.

Methods: For this study, we obtained paired marrow samples at two different time points (initial diagnosis and first complete remission status) in patients with AML. Bone marrow microRNAs were profiled by next-generation small RNA sequencing. Quantification of microRNA expression was performed by counting aligned reads to microRNA genes.

Results: Among 38 samples (32 paired samples from 16 AML patients and 6 normal marrow controls), 27 were eligible for sequencing. Small RNA sequencing showed that 12 microRNAs were selectively expressed at higher levels in AML patients than in normal controls. Among these 12 microRNAs, mir-181, mir-221, and mir-3154 were more highly expressed at initial AML diagnosis as compared to first complete remission. Significant correlations were found between higher expression levels of mir-221, mir-146, and mir-155 and higher marrow blast counts.

Conclusions: Our results demonstrate that mir-221 and mir-181 are selectively enriched in AML marrow and reflect disease activity. mir-3154 is a novel microRNA that is relevant to AML but needs further validation.