Abstract
Splenic marginal zone lymphoma (SMZL) is a low grade, indolent B-cell neoplasm that comprises approximately 10% of all lymphoma. Notch2, a pivotal gene for marginal zone differentiation is found to be mutated in SMZL. Deregulated Notch2 signaling has been involved in tumorigenesis and also in B-cell malignancies. However the role of Notch2 and the downstream pathways that it influences for development of B-cell lymphoma remains unclear. In recent years, RNA sequencing (RNA-Seq) has become a functional and convincing technology for profiling gene expression and to discover new genes and transcripts that are involved in disease development in a single experiment. In the present study, using transcriptome sequencing approach, we have identified key genes and pathways that are probably the underlying cause in the development of B-cell lymphoma. We have identified a total of 15,083 differentially expressed genes (DEGs) and 1067 differentially expressed transcripts (DETs) between control and Notch2 knockdown B cells. Gene Ontology (GO) term enrichment and pathway analysis were applied for the identification of key genes and pathways involved in development of B-cell lymphoma. In addition, intermediate genes of top canonical pathways such as PI3K/AKT and NF-kB were found to be downregulated with Notch2 knockdown, indicating that these pathways could be the putative downstream effectors through which Notch2 mediates its oncogenic effects. Taken collectively, the identified crop of genes and pathways may be considered as targets for the treatment of B-cell lymphoma.
Highlights
Marginal zone lymphomas (MZL’s) are group of indolent B-cell lymphomas that originate from the marginal zone of B-cell follicles
Whole transcriptome analysis was performed in B-cells, where Notch2 expression is knocked down using Notch2-short hairpin RNA (shRNA) and compared with control scramble-shRNA treated cells
A total of 15,083 differentially expressed genes were identified between Notch2-shRNA treated and control samples
Summary
Marginal zone lymphomas (MZL’s) are group of indolent B-cell lymphomas that originate from the marginal zone of B-cell follicles. Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin’s lymphoma (NHL) and it is the most common primary malignancy of the spleen which accounts for ~10% of all lymphomas. It is an uncommon form of NHL that represents less than 1% of new cases [1, 3, 4]. A key regulator for marginal zone differentiation and homing of B cells to the splenic marginal zone were found to be most frequently mutated gene in SMZL [5,6,7,8]. Notch mutations were found to be highly penetrant and specific for marginal zone lymphomas, when compared to other B-cell leukemias and lymphomas [7]
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