Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia

Self Cite

Pediatric acute B-cell lymphoblastic leukemia (B-ALL) constitutes a heterogeneous and aggressive neoplasia in which new targeted therapies are required. Long non-coding RNAs have recently emerged as promising disease-specific biomarkers for the clinic. Here, we identified pediatric B-ALL-specific lncRNAs and associated mRNAs by comparing the transcriptomic signatures of tumoral and non-tumoral samples. We identified 48 lncRNAs that were differentially expressed between pediatric B-ALL and healthy bone marrow samples. The most relevant lncRNA/mRNA pair was AL133346.1/CCN2 (previously known as RP11-69I8.3/CTGF), whose expression was positively correlated and increased in B-ALL samples. Their differential expression pattern and their strong correlation were validated in external B-ALL datasets (Therapeutically Applicable Research to Generate Effective Treatments, Cancer Cell Line Encyclopedia). Survival curve analysis demonstrated that patients with “high” expression levels of CCN2 had higher overall survival than those with “low” levels (p = 0.042), and this gene might be an independent prognostic biomarker in pediatric B-ALL. These findings provide one of the first detailed descriptions of lncRNA expression profiles in pediatric B-ALL and indicate that these potential biomarkers could help in the classification of leukemia subtypes and that CCN2 expression could predict the survival outcome of pediatric B-cell acute lymphoblastic leukemia patients.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia

Cuadros

García

Andrades

et al. 2020

Self Cite

“…The major limitation of this work is the dataset’s low sample size. Unfortunately, few public transcriptomic datasets are available on childhood B–ALL including also healthy subjects (Cuadros et al, 2019 [ 72 ]; Black et al, 2018 [ 50 ]; Lajoie et al, 2017 [ 20 ]). Most of them are not or only partially comparable with our dataset due to (i) different cytogenetics of B–ALL samples; (ii) different high throughput platforms.…”

Section: Discussionmentioning

confidence: 99%

lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

Affinito

Pane

Smaldone

et al. 2020

Long non–coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B–ALL). In this pilot study, we used RNA–Seq transcriptomic data for identifying novel lncRNA–mRNA cooperative pairs involved in childhood B–ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B–ALL lncRNA signatures. We then constructed a co–expression network of the aberrantly expressed lncRNAs (30) and protein–coding genes (754). We cross–validated our in–silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co–expressed mRNAs through ex vivo experiments. Using the guilt–by–association approach, we predicted lncRNA functions based on their perfectly co–expressed mRNAs (Spearman’s correlation) that resulted closely disease–associated. We shed light on 24 key lncRNAs and their co–expressed mRNAs which may play an important role in B–ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B–ALL management.

“…Downregulation of XLOC_109948 in a NPM1-mutated OCI-AML3 cell line treated with Ara-C or ATRA enhanced apoptosis, thus suggesting the role of this lncRNA in drug sensitivity [119]. lncRNAs contribute to proliferation [104,[120][121][122][123][124][125][126], chemoresistance [105,127], and shorter overall survival [128][129][130][131][132] in childhood leukemia, while functions of some highly upregulated and downregulated lncRNAs are still unknown [133], Table 2. Urothelial carcinoma-associated 1 (UCA1) lncRNA was upregulated in some pediatric AML after adriamycin (ADR)-based chemotherapy [105].…”

Section: Long Non-coding Rnamentioning

confidence: 99%

The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia

Elcheva

Spiegelman

2020

RNA molecules are a source of phenotypic diversity and an operating system that connects multiple genetic and metabolic processes in the cell. A dysregulated RNA network is a common feature of cancer. Aberrant expression of long non-coding RNA (lncRNA), micro RNA (miRNA), and circular RNA (circRNA) in tumors compared to their normal counterparts, as well as the recurrent mutations in functional regulatory cis-acting RNA motifs have emerged as biomarkers of disease development and progression, opening avenues for the design of novel therapeutic approaches. This review looks at the progress, challenges and future prospects of targeting cis-acting and trans-acting RNA elements for leukemia diagnosis and treatment.