Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape

Abstract

Lymphocyte migration to and sequestration in specific microenvironments plays a crucial role in their differentiation and survival. Lymphocyte trafficking and homing are tightly regulated by signaling pathways and is mediated by cytokines, chemokines, cytokine/chemokine receptors and adhesion molecules. The production of cytokines and chemokines is largely controlled by transcription factors in the context of a specific epigenetic landscape. These regulatory factors are strongly interconnected, and they influence the gene expression pattern in lymphocytes, promoting processes such as cell survival. The epigenetic status of the genome plays a key role in regulating gene expression during many key biological processes, and it is becoming more evident that dysregulation of epigenetic mechanisms contributes to cancer initiation, progression and drug resistance. Here, we review the signaling pathways that regulate lymphoma cell migration and adhesion with a focus on Mantle cell lymphoma and highlight the fundamental role of epigenetic mechanisms in integrating signals at the level of gene expression throughout the genome.

GSK-J4 Inhibition of KDM6B Histone Demethylase Blocks Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells by Modulating NF-κB Signaling

“…Although our understanding of microenvironment-mediated tumor cell survival and drug resistance has improved, the role of epigenetic mechanisms, especially histone modifications, in this process remains largely unknown [43]. Here, we demonstrate that signals from the tumor microenvironment induce upregulation of NF-κB genes in MCL cells by modifying their histone modification patterns.…”

Lenalidomide regulates the CCL21/CCR7/ERK1/2 axis to inhibit migration and proliferation in diffuse large B-cell lymphoma

“…Chemokines and their receptors play pivotal roles in the progression of various cancers [18]. Studies in B-cell malignancies have revealed subtype-specific patterns of chemokine receptor expression, underscoring their crucial function in the dissemination of malignant B-cells, leading to the formation of monoclonal B-cells and tumor transformation [19,20]. Specifically, in DLBCL, research has highlighted the importance of chemokine receptors.…”

Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma

“…MCL is characterized by the presence of the chromosomal translocation t(11;14) (q13;q32), considered as the genetic hallmark and one of the primary oncogenic events [21,22]. However, this event is not sufficient to confer the full lymphoma phenotype.…”

“…MCL cell survival relies on BCR-mediated signaling and NF-kB pathways [31,32]. Several studies assessed the role of the TME interactions with the tumor B cell in this context, and subsequently the impact of BTK inhibitors [21,29,32]. Indeed, it is now well known that selective inhibition of BTK (or PI3Kdelta) within the BCR (or CXCR4) pathways leads to peripheral lymphocytosis by disrupting the interaction between the TME and tumor B cell and their homing [8,17,33,34].…”