Identification of interconnected markers for T-cell acute lymphoblastic leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a complex disease, resulting from proliferation of differentially arrested immature T cells. The molecular mechanisms and the genes involved in the generation of T-ALL remain largely undefined. In this study, we propose a set of genes to differentiate individuals with T-ALL from the nonleukemia/healthy ones and genes that are not differential themselves but interconnected with highly differentially expressed ones. We provide new suggestions for pathways involved in the cause of T-ALL and show that network-based classification techniques produce fewer genes with more meaningful and successful results than expression-based approaches. We have identified 19 significant subnetworks, containing 102 genes. The classification/prediction accuracies of subnetworks are considerably high, as high as 98%. Subnetworks contain 6 nondifferentially expressed genes, which could potentially participate in pathogenesis of T-ALL. Although these genes are not differential, they may serve as biomarkers if their loss/gain of function contributes to generation of T-ALL via SNPs. We conclude that transcription factors, zinc-ion-binding proteins, and tyrosine kinases are the important protein families to trigger T-ALL. These potential disease-causing genes in our subnetworks may serve as biomarkers, alternative to the traditional ones used for the diagnosis of T-ALL, and help understand the pathogenesis of the disease. © 2013 Emine Guven Maiorov et al.