Exosomes as Liquid Biopsy Biomarkers in Diffuse Large B-cell Lymphoma
(DLBCL)- Current State-of-the-Art and Unmet Clinical Needs
Abstract
Diffuse Large B-Cell Lymphoma is the most common type of Non-Hodgkin’s
Lymphoma. The disease exhibits significant clinical and biologic
heterogeneity. Treatment with standard first line therapy results in
cure in about 60% of patients while 30-40%of patients either are
refractory to therapy or relapse. Current prognostic scores and
biomarkers are unable to accurately predict patients who would relapse
or would have refractory disease. A part of the heterogeneity in the
behavior of DLBCL is explained by the cell of origin of the tumor.
Germinal center type (GCB) DLBCL which is derived from centroblasts are
associated with better prognosis compared with activated B-cell type
(ABC), which is derived from a B-cell committed to secretory
differentiation. While the gold standard for cell of origin
determination is gene expression profiling, immunohistochemical methods
are routinely used because of more readily available fixed tissue and
expertise. Immunohistochemical methods are however associated with a
significant degree of discordance with GEP. Within the ABC and GCB types
of DLBCL, subgroups of prognostic significance have been identified
using various multiple approaches which do not inure themselves to
routine practice partly because of limitation of diagnostic material or
expertise. Exosomes are a class of membrane bound extracellular vesicles
of endosomal origin, produced by multiple cell types. They are involved
in intercellular communication and present in abundance in various
bodily fluids. Exosomal cargo which includes nucleic acids and proteins
can be analyzed, yielding diagnostic and prognostic information in
management of DLBCL.