1/1/2024 0 Comments Active tables for baby![]() First, gene expression profiles are considered to identify DC gene pairs and construct a DC network between GC-resistance and GC-sensitive conditions. In this study, we propose the use of DC analysis to identify protein modules that are active in GC-resistance infant ALL patients but not in GC-sensitive patients. Prior to such approach, protein-protein interaction (PPI) networks have been used to find disease-specific protein modules enriched with differentially expressed genes between two groups of samples (Ideker et al. Instead of gene modules, some studies used DC analysis to find phenotype-specific protein modules (Zhang et al. The detected module included genes with documented association to GC-resistance, confirming the hypothesis that network-based analysis complements the conventional gene-wise methods and provides further biological insights into GC-resistance in MLL-rearranged infant ALL. Motivated by the fact that gene differential co-expression (DC) analysis has emerged as an alternative approach to differential expression analysis (de la Fuente 2010), recently we used weighted gene co-expression network analysis to reveal a gene module associated with GC-resistance (Mousavian et al. The majority of gene expression studies adopted conventional gene-wise approaches that detect differential expression in each gene separately between two phenotypes. 2014b), knowledge regarding the mechanism underlying this phenomenon remains limited. Although some researchers have found biomarkers that mediate GC-resistance in MLL-rearranged infant ALL (Spijkers-Hagelstein et al. Glucocorticoids are used in ALL treatment for their cytotoxicity induction properties that lead to cellular apoptosis (Gaynon and Carrel 1999) and resistance to their effects is the main cause of treatment failure in MLL-rearranged infant ALL (Pieters et al. This condition is associated with a genetic translocation involving the mixed lineage leukemia (MLL) gene (gene KMT2A) that is present in about 80% of infant ALL patients (Greaves 1996 Pieters et al. However, the treatment outcome remains poor in infant (< 1 year of age) ALL patients due to frequent resistance to cytotoxic chemotherapy drugs, including glucocorticoids (GCs). ALL is the most common type of leukemia in children (Gaynon and Carrel 1999) and major improvements in the treatment of childhood ALL have been achieved in recent years (Pui et al. Functional enrichment analysis of detected protein modules generates new biological hypotheses and may help in explaining the GC-resistance in MLL-rearranged infant ALL patients.Īcute lymphoblastic leukemia (ALL) is a malignant disease of the bone marrow characterized by the overproduction of immature white blood cells that accumulate and inhibit the production of normal cells. The approach allows the detection of relevant protein modules that are highly enriched with DC gene pairs. Conclusionsĭifferential co-expression analysis is a promising approach to incorporate the dynamic context of gene expression profiles into the well-documented protein interaction networks. These findings are in accordance with previous findings related to GC-resistance in other hematological malignancies such as pediatric ALL. Functional enrichment analysis revealed that these modules are related to proteasome, electron transport chain, tRNA-aminoacyl biosynthesis, and peroxisome signaling pathways. ![]() Through the integration of DC analysis and PPI network, four protein modules were found active under the GC-resistance phenotype but not under the GC-sensitive. Finally, both sub-networks were clustered into modules using weighted gene co-expression network analysis (WGCNA) and further analyzed with functional enrichment analysis. The resulting network was decomposed into two sub-networks, specific to each phenotype. A network was constructed by linking differentially co-expressed gene pairs between GC-resistance and GC-sensitive samples and later integrated with PPI networks by keeping the links that are also present in the PPI network. ![]() This study integrates differential co-expression (DC) and protein-protein interaction (PPI) networks to find active protein modules associated with GC-resistance in MLL-rearranged infant ALL patients. Although some studies examined GC-resistance in infant ALL patients, the understanding of this phenomenon remains limited and impede the efforts to improve prognosis. The category of infant ALL patients carrying a translocation involving the mixed lineage leukemia (MLL) gene (gene KMT2A) is characterized by resistance to GCs and poor clinical outcome. Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children and Glucocorticoids (GCs) form an essential component of the standard chemotherapy in most treatment regimens.
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