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Published on: September 1, 2019
Expression of long non-coding RNA UCA1 and its clinical relevance in paediatric acute myeloid leukemia
Christine Wilson1, Diwakar Sharma1, Priyanka Swaroop2
1Department of Medical Oncology, All India Institute of Medical Sciences New Delhi, India.
Abstract:
The underlying mechanisms and clinical significance of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is largely unknown in acute myeloid leukemia (AML). We aimed to study the expression of lncRNA UCA1, and its biological and clinical relevance in AML. Expression of lncRNA UCA1 was quantified in peripheral blood (PB) samples of children with de novo AML (n=69), post-induction, after achieving complete remission (CR) (n=8), and in patients who had relapsed (n=10). Additionally, two external cohorts were analysed i.e., TCGA-LAML dataset and Leukemia-MILE study. We also quantified expression in four different AML cell lines and analysed expression after cell differentiation. A consistent pattern of low UCA1 expression in AML was observed in our cohort of sixty-nine patients at baseline (P < 0.0001) and in the TCGA and Leukemia-MILE datasets. In patients who achieved remission, expression was comparable to healthy individuals, while relapsed patients interestingly had lower levels of UCA1 (P=0.0002). Furthermore, lncRNA UCA1 expression was significantly lower in AML cell lines (THP-1, P=0.0112; KG-1, P=0.0168; and HL-60, P=0.0112) and increased when THP-1 cells were differentiated (P=0.0001). In our AML patient cohort, lower expression was significantly associated with CR (P=0.043), however, the impact on survival (EFS and OS) was not significant. This is the first study wherein the lncRNA UCA1 expression was studied in various AML cell lines along with AML patients at baseline, remission and relapse. In conclusion, we found that UCA1 is significantly downregulated in AML compared to healthy individuals and mature differentiated cells.
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