Dataset Information

Novel Markers in Pediatric Acute Lymphoid Leukemia: The Role of ADAM6 in B Cell Leukemia.

ABSTRACT:

Background

The extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out in silico analysis of publicly available ALL datasets to identify genetic biomarkers for childhood BCP-ALL, which could be used either individually or in combination as markers for early detection, risk stratification, and prognosis.

Methods

To explore novel genes that show promising clinical and molecular signatures, we examined the cBioPortal online tool for publicly available datasets on lymphoid cancers. Three studies on lymphoblastic and lymphoid leukemia with 1706 patients and 2144 samples of which were identified. Only B-Lymphoblastic Leukemia/Lymphoma samples (n = 1978) were selected for further analysis. Chromosomal changes were assessed to determine novel genomic loci to analyze clinical and molecular profiles for the leukemia of lymphoid origin using cBioPortal tool.

Results

ADAM6 gene homozygous deletions (HOM:DEL) were present in 59.60% of the profiled patients and were associated with poor ten years of overall patients' survival. Moreover, patients with ADAM6 HOM:DEL showed a distinguished clinical and molecular profile with higher Central Nervous System (CNS) sites of relapse. In addition, ADAM6 HOM:DEL was significantly associated with unique microRNAs gene expression patterns.

Conclusion

ADAM6 has the potential to be a novel biomarker for the development and progress of BCP- ALL.

SUBMITTER: Alsuwaidi L

PROVIDER: S-EPMC8269160 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPediatric T-cell acute lymphoblastic leukemia (T-ALL) poses significant challenges due to its aggressive nature and resistance to standard treatments. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers and therapeutic targets in leukemia. This study aims to characterize the lncRNA landscape in pediatric T-ALL, identify specific lncRNAs signatures, and assess their clinical relevance.MethodsRNA sequencing was performed on T-ALL patient and control samples. Differential expression analysis identified dysregulated lncRNAs and mRNAs. Functional enrichment analysis revealed potential roles of these lncRNAs in cancer pathogenesis. Validation of candidate lncRNAs was conducted using real-time PCR. Clinical correlations were assessed, including associations with patients' clinical characteristics and survival outcomes.ResultsAnalysis identified 674 dysregulated lncRNAs in pediatric T-ALL, with LINC01221 and CRNDE showing the most interactions in cancer progression pathways. Functional enrichment indicated involvement in apoptosis, survival, proliferation, and metastasis. Top 10 lncRNAs based on adjusted p value < 0.05 and Fold Change > 2 were selected for validation. Seven lncRNAs LINC01221, PCAT18, LINC00977, RP11-620J15.3, RP11-472G21.2, CTD-2291D10.4, and CRNDE showed correlation with RNA sequencing data. RP11-472G21.2 and CTD-2291D10.4 were highly expressed in T-ALL patients, with RP11-620J15.3 correlating significantly with better overall survival (p = 0.0007) at a median follow up of 32 months. The identified lncRNAs were further analysed in B-ALL patients. Distinct lncRNAs signatures were noted, distinguishing T-ALL from B-ALL and healthy controls, with lineage-specific overexpression of LINC01221 (p < 0.0001), RP11-472G21.2 (p < 0.001) and CRNDE (p = 0.04) in T-ALL.ConclusionThis study provides insights into the lncRNA landscape of pediatric T-ALL, offering potential diagnostic and prognostic markers. RP11-620J15.3 emerges as a promising prognostic marker, and distinct lncRNAs signatures may aid in the differentiation of T-ALL subtypes. Further research with larger cohorts is warranted to validate these findings and advance personalized treatment strategies for pediatric T-ALL patients.