Comparative Transcriptomic Analysis of ATRA-Resistant and ATRA-Sensitive APL Cell Lines Identifies LncRNA Biomarkers Associated with Drug Resistance

Abstract

Acute promyelocytic leukemia is a distinct subtype of acute myeloid leukemia characterized by the t(15;17) translocation, leading to the PML (Promyelocytic leukemia protein)-RARA (Retinoic Acid Receptor Alpha) fusion protein. Although PML-RARA fusion is common, there are 20 more fusion events also reported in APL. All -trans retinoic acid (ATRA) is a standard drug for APL, leading to significant improvement in patient outcomes; nevertheless, a small fraction of patients still experience relapse, and some patients exhibit resistance to the drug. Long non-coding RNAs (LncRNAs) are recognized as promising biomarkers for cancer diagnosis, prognosis, and treatment response. In this study, we used ATRA-Resistant (AP1060) and ATRA -Sensitive (NB4), both treated and untreated cell line transcriptomic data retrieved from the NCBI Gene Expression Omnibus(GEO) database to perform transcriptomic analysis with bioinformatic tools. We utilized the LncRAnalyzer pipeline to predict the lncRNAs, followed by differential expression analysis using DESeq2. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct lncRNA co-expression modules associated with ATRA resistance. BEDTools is used to identify cis-acting target genes of lncRNAs.LncRNA -miRNA sponging identified by miRanda algorithm. The identified miRNAs reveal their significant role in APL and other leukemia subtypes. The results of the study show that the identified lncRNAs from the miRNA-LncRNA network are promising biomarkers for ATRA resistance.