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Pathogenesis

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.

References

  1. Sun R, Medeiros LJ, Young KH. Diagnostic and predictive markers for lymphoma diagnosis and treatment in the era of precision medicine. Mod Pathol. 2016;29:1118-1142. doi:10.1038/modpathol.2016.92
  2. Nogai H, Dörken B, Lenz G. Pathogenesis of non-Hodgkin’s lymphoma. J Clin Oncol. 2011;29:1803-1811. doi:10.1200/JCO.2010.33.3252
  3. Fisher RI, Oken MM. Clinical practice guidelines: Non-Hodgkin’s lymphomas. Cleve Clin J Med. 1995;62(suppl 1):SI-6–SI-42. (https://www.ccjm.org/content/ccjom/62/1_suppl_1/SI-6.full.pdf).
  4. Forsthuber TG, Cimbora DM, Ratchford JN, Katz E, Stüve O. B cell-based therapies in CNS autoimmunity: Differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord. 2018;11:1756286418761697. doi:10.1177/1756286418761697
  5. Lodhi N, Tun M, Nagpal P, et al. Biomarkers and novel therapeutic approaches for diffuse large B-cell lymphoma in the era of precision medicine. Oncotarge 2020;11:4045-4073. doi:10.18632/oncotarget.27785

All URLs accessed July 1, 2024

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