Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia

Farrar JE, Smith JL, Othus M, Huang BJ, Wang YC, Ries R, Hylkema T, Pogosova-Agadjanyan EL, Challa S, Leonti A, Shaw TI, Triche TJ Jr, Gamis AS, Aplenc R, Kolb EA, Ma X, Stirewalt DL, Alonzo TA, Meshinchi S. Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2023 Jun 1;41(16):2949-2962. doi: 10.1200/JCO.22.01114. Epub 2023 Feb 16. PubMed PMID: 36795987; PubMed Central PMCID: PMC10414715.

Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML. To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis.