A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia

Hale, Victoria; Hale, Gregory A.; Brown, Patrick; Amankwah, Ernest K.

doi:10.1159/000452091

Cited by 22 publications

(14 citation statements)

References 58 publications

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“…Previous studies have suggested the association between pediatric ALL relapse and miRNAs, such as miR-24, miR-128b, miR-223, miR-210, miR-335, miR-130b, miR-126, miR-222, miR-345, miR-708 and miR-23a (14). However, none of the six candidate miRNAs in this study have been previously implicated in pediatric B-ALL relapse.…”

Section: Discussioncontrasting

confidence: 65%

Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia

et al. 2020

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Background/Aim: Few studies have evaluated the role of miRNAs in pediatric acute lymphoblastic leukemia (ALL) relapse and a consensus of a clinically significant miRNA signature is yet to be identified. In this study, we evaluated miRNAs associated with pediatric BALL early relapse in two independent sample sets. Materials and Methods: We performed global miRNA profiling on diagnostic bone marrow specimens from six early relapse (≤3 years after diagnosis) and six age-and cytogenetics-matched prolonged remission (≥4 years) patients (first set) and an independent set of 14 early relapse and 14 matched prolonged remission specimens (second set). Results: Twelve and 39 top differentially expressed miRNAs were observed in the first and second sets, respectively; however, there was no overlap between the top candidates. In post-hoc analyses six miRNAs (miR-101-3p, miR-4774-5p, miR-1324, miR-631, miR-4699-5p and miR-922) among the top candidates in the second, but not the first set, were consistently upregulated in early relapse compared to remission specimens in both first (fold change=1.13-2.19, q<0.38) and second (fold change=1.48-4.78, all q<0.05) sets. Four (miR-631, mir-101-3p, miR-922 and miR-1324) of these miRNAs have been previously implicated in key functional oncogenic pathways in adult cancers. Conclusion: This study suggests that six candidate miRNAs, not previously implicated in pediatric ALL, are associated with early relapse in pediatric BALL. Validation and investigation of mechanistic roles of these miRNAs in a larger cohort are warranted, so that they may be used as prognostic markers for early relapse of pediatric BALL. Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed among children, accounting for a quarter of all cancer diagnoses and three-quarters of childhood leukemia diagnoses (1, 2). The 5-year and overall survival rates of ALL have increased over the years to approximately 80% and 85%, respectively (1-3), largely due to risk-stratification and combination chemotherapy (4, 5). However, 10-15% of patients develop recurrence and, depending on the recurrence site, 5-50% will survive with only a third surviving long-term (6-9). Knowledge on the mechanism of leukemia relapse is still limited (10-13). Few studies have evaluated the association between miRNA expression and pediatric ALL relapse (14). Although these studies have identified potential prognostic miRNAs, a consensus of a clinically significant miRNA signature is yet to be identified. In addition, several previous studies have investigated a limited number (n=1-723) of miRNAs (15-20) or have not included an independent replication dataset (17, 18). In this study, we provide additional evidence for the association between miRNAs and pediatric BALL early relapse by investigating a large number of miRNAs (~2,600 human miRNAs) in two independent sample sets. Materials and Methods Patient accrual and sample collection. The study included two independent preselected sets of patients. The first set consisted of six patients ...

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Section: Discussioncontrasting

confidence: 65%

Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia

et al. 2020

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“…Besides the metabolic and catabolic process of 5-methylcytosine was also enriched. This indicated that methylation activity in cells administrated by PQ might be enhanced, and DNA methylation could further affect gene expression by regulating miRNA synthesis (Hale et al, 2017). Otherwise, according to pathway analysis, PI3K-Akt, mTOR, RAS, TNF and MAPK signaling pathways were significantly enriched.…”

Section: Discussionmentioning

confidence: 96%

Analysis of microRNA expression profiling during paraquat-induced injury of murine lung alveolar epithelial cells

et al. 2020

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Paraquat (PQ) as a non-selective heterocyclic herbicide, has been applied worldwide for over a few decades. But PQ is very harmful to humans and rodents. The lung is the main target organ of PQ poisoning. It is an important event that lung epithelial cells are injured during PQ-induced acute lung injury and pulmonary fibrosis. As a regulator of mRNA expression, microRNA (miRNA) may play an important role in the progress. Our study was to investigate the mechanisms of PQ-induced injury of pulmonary epithelial cells through analyzing the profiling of miRNAs and their target genes. As a result, 11 differentially expressed miRNAs were screened, including 1 upregulated miRNA and 10 downregulated miRNAs in PQ-treated murine lung alveolar epithelial cells (MLE-12 cells). The bioinformatic analyses suggested that the target genes of these miRNAs were involved in mitochondrial apoptosis pathway and DNA methylation, and participated in the regulation of PI3K-Akt, mTOR, RAS, TNF, MAPK and other signal pathways which related to oxidative stress and apoptosis. This indicated that miRNAs were an important regulator of oxidative stress and apoptosis during PQ-induced injury of murine lung alveolar epithelial cells. The findings would deepen our understanding of the mechanisms of PQ-induced pulmonary injury and might provide new treatment targets for this disease.

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“…Aberrant epigenome has been implicated in the undesired treatment outcomes of children with B-ALL. 25,26 A study conducted on 33 pairs of samples, which were collected at diagnosis and relapse, found that DNA hyper-methylation was a hallmark of relapse samples; 905 genes were hyper-methylated in relapsed pediatric B-ALL. 27 The same study showed that different regulators of Wnt pathway and tumor suppressor genes were amongst the hyper-methylated genes.…”

Section: Omics-based Insights Into Therapy Failure In Patients With Pmentioning

confidence: 99%

Omics-based insights into therapy failure of pediatric B-lineage acute lymphoblastic leukemia

Alsagaby

2019

Oncol Rev

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B-lineage acute lymphoblastic leukemia (B-ALL) is the most common type of cancer seen in children and is characterized by a variable clinical course. Although there have been remarkable improvements in the therapy outcomes of pediatric B-ALL, treatment failure remains the leading-cause of death in 18% of the afflicted patients during the first 5 years after diagnosis. Molecular heterogeneities of pediatric B-ALL play important roles as determinants of the therapy response. Therefore, many of these molecular abnormalities have an established prognostic value in the disease. The present review discusses the omics-based revelations from epigenomics, genomics, transcriptomics and proteomics about treatment failure in pediatric B-ALL. Next it highlights the promise of the molecular aberration-targeted therapy to improve the treatment outcomes.

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A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia

Cited by 22 publications

References 58 publications

Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia

Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia

Analysis of microRNA expression profiling during paraquat-induced injury of murine lung alveolar epithelial cells

Omics-based insights into therapy failure of pediatric B-lineage acute lymphoblastic leukemia

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