Lymphoma is a diverse group of blood cancer that arise in the lymphatic system, which are generally classified into two groups: Hodgkin lymphoma is characterized by multinucleated giant Reed-Sternberg cells, an abnormal type of B cells, which are surrounded by a large number of mononucleated Hodgkin cells. Hodgkin´s lymphoma are one of the most curable forms of cancer and are usually treated by chemotherapy and radiation. The second group, Non-Hodgkin Lymphoma (NHL), are further classified by the cell type they originate in, which in most cases (85%) are B-cells, but may also arise in T- or NK-cells.
Most B-cell lymphomas, arise in the germinal centres (GC), transient structures that form in lymphoid tissues by presentation of a T-cell dependent antigen to a mature naïve B-cell, resulting in B-cell differentiation and the generation of memory B-cells and plasma cells. The GC reaction begins with a rapidly dividing B-cell population, called centroblasts, which undergo class-switch recombination and somatic hypermutation to switch the immunoglobulin heavy-chain class and create a multitude of immunoglobulin variable regions that show distinct affinities to the immunizing antigen that are later on selected for by a process called affinity maturation. These processes are essential to humoral immunity, yet contribute to chromosomal translocations and DNA-damage and thus to lymphomagenesis. GC B-cells give rise to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma or Burkitt´s lymphoma, which share features of their differentiation state such as expression of the transcription factor BCL-6 or ongoing somatic hypermutation (SHM). The normal cellular program however is disrupted by genetic mechanisms, for example translocation of the antiapoptotic protein BCL-2 leads to its aberrant expression and evasion of apoptosis. Similarly, antiapoptotic signaling is enhanced by constitutive activation of NF-kB. The Myc oncogene is often translocated or amplified, by which it evades negative regulation by Bcl-6, allowing MYC to potently contribute to cell growth and metabolic reprogramming.
The most common form of aggressive lymphoma is diffuse large B-cell lymphoma (DLBCL), which accounts for about one third of newly diagnosed NHL. The complex genetic landscape of DLBCL compared to other lymphomas is probably responsible for treatment failure or relapse, which occur in 30% of patients.
TICC Faculty who are involved in Lymphoma research:
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