Deciphering the Non-Coding RNA Landscape of Pediatric Acute Myeloid Leukemia

Abstract

Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20–30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.

Long non-coding RNAs: emerging functional players in the pathobiology and progression of myeloid leukemia

“…There are several examples of lncRNAs that have been characterized in pediatric AML that show correlations to patient prognosis and survival; such examples were summarized in a recent review by Neyazi et al (2022). In a recent comprehensive study, Vanhooren et al (2022) performed a miRNA-lncRNA network analysis in leukemic stem cells (LSCs) and leukemic blasts (L-blasts) from pediatric AML patients; this study identified several novel lncRNAs and miRNAs in pediatric AML that could become new biomarkers for risk stratification and targeted therapy in the future. Using RNA-seq data from normal bone marrow and de novo AML pediatric patient samples, followed by regularized Cox proportional hazards modeling of the event-free survival (EFS), Farrar et al ( 2022) calculated a 37-gene lncScore that showed a significant correlation with patient survival.…”

Non-Coding RNAs: Foes or Friends for Targeting Tumor Microenvironment

“…It has been presented that the expression of 22 lncRNAs was substantially changed in leukemic stem cells compared to hematopoietic stem cells in pediatric AML samples. The findings from these studies offer new avenues for addressing pediatric AML through targeted treatments [135]. In the same year, Li et al analyzed the expression of lncRNA and mRNA in B-ALL samples using the RNA sequencing method.…”

Therapeutic Targeting of TIM-4-L with Engineered T Cells for Acute Myeloid Leukemia

“…Development of engineered T cell therapies for acute myeloid leukemia (AML), a clinically and biologically heterogenous disease, has proven difficult in part due to the identification of suitable target antigens (1)(2)(3)(4). Epigenetic profiling has revealed diverse alterations in AML (5), notably the dysregulation of key lipid transport molecules that drive immunosuppression and maintain lipid composition and structure within plasma membranes (6).…”