Genomics of lymphoid malignancies reveal major activation pathways in lymphocytes.

J Autoimmun
Authors
Keywords
Abstract

Breakdown of tolerance leads to autoimmunity due to emergence of autoreactive T or B cell clones. Autoimmune diseases predispose to lymphoid malignancies and lymphoid malignancies, conversely, can manifest as autoimmune diseases. While it has been clear for a long time that a competitive advantage and uncontrolled growth of lymphocytes contribute to the pathogenesis of both lymphoid malignancies as well as autoimmune diseases, the overlap of the underlying mechanisms has been less well described. Next generation sequencing has led to massive expansion of the available genomic data in many diseases over the last five years. These data allow for comparison of the molecular pathogenesis between autoimmune diseases and lymphoid malignancies. Here, we review the similarities between autoimmune diseases and lymphoid malignancies: 1) Both, autoimmune diseases and lymphoid malignancies are characterized by activation of the same T and B cell signaling pathways, and dysregulation of these pathways can occur through genetic or epigenetic events. 2) In both scenarios, clonal and subclonal evolution of lymphocytes contribute to disease. 3) Development of both diseases not only depends on T or B cell intrinsic factors, such as germline or somatic mutations, but also on environmental factors. These include infections, the presence of other immune cells in the microenvironment, and the cytokine milieu. A better mechanistic understanding of the parallels between lymphomagenesis and autoimmunity may help the development of precision treatment strategies with rationally designed therapeutic agents.

Year of Publication
2013
Journal
J Autoimmun
Volume
45
Pages
15-23
Date Published
2013 Sep
ISSN
1095-9157
URL
DOI
10.1016/j.jaut.2013.06.012
PubMed ID
23880067
PubMed Central ID
PMC3839094
Links
Grant list
T32 HL007574 / HL / NHLBI NIH HHS / United States