Lymphoma biology notes
Normal B cell biology
BCL2 is a transcription factor promoting proliferation. It is upregulated within the germinal centre
BCL6 is an apoptotic protein, helping cells to die naturally. It is downregulated within the germinal centre.
C-MYC, located on chromosome 8, is a ‘global’ transcription factor with roles in proliferation and cellular growth. Under normal conditions it is able to induce apoptosis.
Most lymphomas are IgM B cells and go through a number of molecular steps to maintain IgM expression, which appears to be linked to malignant cell survival.
Hence why IgM MGUS behaves as lymphoplasmacytic lymphoma, where other MGUS moves to myeloma.
Germinal Centre (CD10+) Lymphomas include:
Burkitts (forced MYC expression with B cell receptor signaling)
DLBCL is the most common haematological malignancy. One explanation is that cancer is likely to arise more commonly out of the germinal centres, where the process of class switching and somatic hypermutation opens up the risk of erroneous malignant mutations. To compound the risk, normal DNA repair mechanisms are down regulated in the germinal centres to expedite theses processes.