Transcriptome Analysis Identifies LINC00152 as a Biomarker of Early Relapse and Mortality in Acute Lymphoblastic Leukemia

Abstract

Evidence showing the role of long non-coding RNAs (lncRNAs) in leukemogenesis have emerged in the last decade. It has been proposed that these genes can be used as diagnosis and/or prognosis biomarkers in childhood acute lymphoblastic leukemia (ALL). To know if lncRNAs are associated with early relapse and early mortality, a microarray-based gene expression analysis in children with B-lineage ALL (B-ALL) was conducted. Cox regression analyses were performed. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. LINC00152 and LINC01013 were among the most differentially expressed genes in patients with early relapse and early mortality. For LINC00152 high expression, the risks of relapse and death were HR: 4.16 (95% CI: 1.46–11.86) and HR: 1.99 (95% CI: 0.66–6.02), respectively; for LINC01013 low expression, the risks of relapse and death were HR: 3.03 (95% CI: 1.14–8.05) and HR: 6.87 (95% CI: 1.50–31.48), respectively. These results were adjusted by NCI risk criteria and chemotherapy regimen. The lncRNA–mRNA co-expression analysis showed that LINC00152 potentially regulates genes involved in cell substrate adhesion and peptidyl–tyrosine autophosphorylation biological processes. The results of the present study point out that LINC00152 could be a potential biomarker of relapse in children with B-ALL.

Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

“…When comparing ID to REL samples within each subtype studied, 570, 113, and 248 lncRNAs were differential in DUX4 , Ph-like, and in NH-HeH samples respectively. Other studies have shown that LINC00152 and LINC01013 were among the most differentially expressed genes in patients with early relapse of disease compared to healthy controls [ 76 ]. Specifically, higher expression of LINC00152 in children with B-ALL was associated with a higher risk of early relapse; conversely, lower expression of LINC01013 was associated with early relapse.…”

Differential mRNA and Long Noncoding RNA Expression Profiles in Pediatric B-Cell Acute Lymphoblastic Leukemia Patients

“…Previous studies regarding the transcriptic results of B-ALL patients have identi ed a number of lncRNAs and vital protein-coding genes that are associated with the etiology or clinical outcome of B-ALL [17][18][19]. To the best of the authors' knowledge, although some studies have performed transcriptome pro le analysis to investigate the role of lncRNA in the pathogenesis of B-ALL, the small sample sizes of parallel their controls and the restricted numbers of isolated cell types limited the general conclusions of these studies [20][21][22]. Moreover, microarray data prevented the identi cation of novel transcripts.…”

Identification of Early Recurrence Factors in Childhood and Adolescent B-Cell Acute Lymphoblastic Leukemia Based on Integrated Bioinformatics Analysis

“…MLL rearranged, hypodiploid, BCR/ABL fusion gene and high end-induction MRD are the common risk factors for relapse in childhood ALL patients ( 19 ). And several published articles showed that the biomarkers for early recurrence in B-ALL include the persistence of MRD, chromosome 19p13 translocations, upregulation of nucleotide excision repair genes, deletion of CDKN2A/B and overexpression of LINC00152 ( Supplementary Table S1 ) ( 20 – 24 ). In this study, we looked for genes involved in early relapse of B-ALL on a larger sample.…”