Most NHL cancers are associated with chromosomal abnormalities, originating within a single cell, with subsequent cells carrying the identical variation.1 As such, lymphomas arise at different stages of B-cell differentiation. Specific recombination events lead to the development of chromosomal aberrations. The germinal center is surrounded by a mantle zone of naive B cells, most of which express the CD5 marker which might comprise a distinct B-cell subset. Recombination activating gene 1 (RAG1)-dependent and RAG2-dependent V(D)J recombination takes place in the bone marrow. The potentially resulting t(14;18) and t(11;14) represent critical first steps in lymphomagenesis of different lymphoma subtypes. After antigen contact, the stimulated B cells migrate to the lymph node and form the germinal center after upregulation of BCL6. The events during the germinal center reaction include activation-induced cytidine deaminase (AID) –mediated somatic hypermutation and class-switch recombination, which are critical events for lymphoma evolution. The germinal center reaction is terminated by the differentiation of B cells into plasma cells. XBP1 and Blimp-1 are key regulators for plasmacytic differentiation.1-3
Various recurrent genomic and molecular biomarkers are involved in B-cell lymphomas, with prognostic effects related to various genetic abnormalities in proteins including MYC, BCL2, BCL6, TP53, etc.1 Additionally, development of unique anti-CD antibodies for treatment of specific lymphomas is possible due to specific biomarker expression at each stage of B-cell development and differentiation.
Taking CD20 expression as an example, it is largely restricted to B-cells and certain stages of their development; pro-B cells, differentiated plasmablasts or plasma cells do not express CD20. Furthermore, CD-20 is detected in approximately 95% of all B-cell malignanices.4 The table below outlines various microenvironment-related biomarkers in lymphoma prognosis that can be used to predict the clinical outcome of patients, as well as how to detect them.
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