Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes

非编码 RNA 及其对接受阿扎胞苷治疗的骨髓增生异常综合征患者和伴有骨髓增生异常相关改变的急性髓系白血病患者的反应预测价值

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作者:Michaela Dostalova Merkerova, Jiri Klema, David Kundrat, Katarina Szikszai, Zdenek Krejcik, Andrea Hrustincova, Iva Trsova, Anh Vu LE, Jaroslav Cermak, Anna Jonasova, Monika Belickova

Aim

Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs). Materials and

Conclusion

The expression of various ncRNAs can influence the effect of AZA and new ncRNA-based predictive biomarkers can be defined.

Methods

RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers.

Results

Our analyses showed that lncRNAs had the strongest predictive potential. The combined set of the best predictors included 14 lncRNAs, and only four PCGs, one circRNA, and no TEs. Epigenetic regulation and recombinational repair were suggested as crucial for AZA response, and network modeling defined three deregulated lncRNAs (CTC-482H14.5, RP11-419K12.2, and RP11-736I24.4) associated with these processes.

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