Abstract
ETV6/RUNX1 gene fusion is the most common chromosomal translocation abnormality occurred in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Compared with ETV6-RUNX1-negative patients, ETV6-RUNX1-positive patients possess more improved treatment strategies but higher risk to relapse. In this research, the potential gene interaction networks were constructed intending for elucidating the pathogenesis of B-ALL. We performed the weighted gene co-expression network analysis (WGCNA) to assess the involvement of lncRNA-mRNA pairs in B-ALL patients consisting of 24 ETV6-RUNX1-positive patients and 18 ETV6-RUNX1-negative patients and found a module that was significantly associated with positive/negative trait. Gene Ontology analysis showed that mRNAs in this module were enriched in the positive regulation of MAPK cascade, positive regulation of JNK cascade, and myeloid cell differentiation pathway. To further investigate the relationship between lncRNAs and mRNAs in this significant module, we constructed the lncRNA-mRNA co-expression network. 3 lncRNAs (RP11-170J3.2, RP11-135F9.1 and RP1-151B14.9) were found at the core of the lncRNA-mRNA co-expression network, which had the most co-expression connections with mRNAs. And several related mRNAs (ACTN1, TNFRSF21 and NLRP3) had a significant correlation with the patient survival prediction. Our findings may explicate the pathogenesis of B-ALL, and the disease-associated genes could provide clues to find novel biomarkers for prognosis.
Highlights
Acute lymphoblastic leukemia (ALL), a type of blood cancer, is the most common malignancy diagnosed in children worldwide [1], with about 90% 5-year survival rate in children, and 75– 85% in adolescents and young adults [2,3,4]
Previous researches have conducted the comprehensive profiles of Long non-coding RNAs (lncRNAs) in pediatric B-cell acute myeloid leukemia (B-ALL) by RNA microarray [32,33], while the mRNAs associated with lncRNAs have not been illustrated
We found that ACTN1, TNFRSF21 and NLRP3 had a significant correlation with the ALL patient survival prediction
Summary
Acute lymphoblastic leukemia (ALL), a type of blood cancer, is the most common malignancy diagnosed in children worldwide [1], with about 90% 5-year survival rate in children, and 75– 85% in adolescents and young adults [2,3,4]. The outcomes are worse in older adults, with an overall survival rate of 35–55% in middle-aged people and below 30% in people over 60 [5,6]. The hallmark of ALL is driven by a spectrum of genetic aberrations including mutations, chromosome translocations and aneuploidy in genes involved in differentiation and proliferation of B-lineage or T-lineage lymphoid precursor cells [7].
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