Expression levels of
long non-coding RNA (
lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal
acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of
lncRNA in AML patients is unknown. Herein, we analyzed total
RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in
lncRNA that are expressed in leukemic blasts. Among these variants, we identified a
cytosine-to-
thymidine variant in the
lncRNA RP5-1074L1.4 and a
cytosine-to-
thymidine variant in the
lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15
cytosine-to-
thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and
RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15
lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the
cytosine-to-
thymidine variant. We conclude that recurrent genetic variants of
lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.