Histone-, Receptor-, and Integrin-Related Gene Products and ADAM28 as Relevant to B-Cell Acute Lymphoblastic Leukemia (B-ALL).

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with pediatric ALL having a ~90 percent cure rate, while the adult cure rate is considerably lower. B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of ALL and is generally treated through a variety of chemotherapy drugs that can cause undesired side effects, adverse events, or other complications. Consequently, there is a need for improved understanding of the shared gene expression profiles and underlying molecular mechanisms shared among various B-ALL subtypes. In this study, 259 publicly available RNA-sequencing samples were evaluated and retrieved from the NCBI Gene Expression Omnibus (GEO) database and then pre-processed using a robust computational workflow. Differential gene expression, pathway enrichment, marker prediction, and drug repurposing analyses were then performed to facilitate a better mechanistic understanding of disease. We found both previously identified as well as novel differentially expressed genes. Specifically, we observed upregulation in the HIST2H2AA3, EPHA7, and MPR1 genes; while downregulation was observed for the IGHA1, ANGPTL1, and CHAD genes. We identified multiple pathways, including "Integrins in Angiogenesis", to be significantly affected in B-ALL. We then used these significant pathways to predict and rank 306 existing therapeutic targets that could potentially be repurposed for B-ALL, including three that have not been evaluated in human clinical trials. Using a tree-based classification algorithm, we also predicted ADAM28 as a possible mechanistic marker. The results of this study have potential implications for patients who have been diagnosed with B-ALL by providing improved mechanistic understanding and information on possible diagnostics and repurposed therapeutics for B-ALL.