A Possible Risk Gene for B-cell Chronic Lymphocytic Leukemia: NRIP1

Abstract

Background: The underlying mechanisms that cause B-cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, remain unclear. The aim of this study is to investigate the novel genetic risk of B-CLL through systematic literature review and metaanalysis. Methods:A comprehensive search of electronic databases was completed using Illumina BioEngine. Twenty one B-CLL case/control bio-sets from four different studies were selected, including 195 B-CLL cases and 31 controls. The selected top B-CLL risk genes were further analyzed by integrating an online open source B-CLL genetic database. Pathway enrichment analysis (PEA) and network connectivity analysis (NCA) were conducted to identify the potential functional association between target genes and B-CLL. Results:One novel gene (NRIP1) and two known genes (INPP5F and LEF1) were identified through the meta-analysis as top target genes for B-CLL. These genes play important roles within multiple B-CLL genetic pathways and are closely related to known B-CLL target genes. NCA results also revealed strong functional association between these genes and B-CLL. Conclusion:This study identified known as well as novel B-CLL target genes and their functional pathways that involved in the B-CLL pathogenesis. Our results may provide new insights into the understanding of the genetic mechanisms of B-CLL.