This patient’s combination of “B”-symptoms (fever, weight loss, fatigue) and a hard neck mass with a t([14;18]) translocation is diagnostic for follicular lymphoma. The chromosomal translocation (t[14;18]) results in upregulation of the antiapoptotic factor Bcl-2. Bcl-2, along with Bcl-xL, prevents the release of cytochrome c and stops it from binding to APAF-1 and activating the caspase cascade, which results in apoptosis. In B-lymphocyte malignancies, particularly follicular lymphoma, upregulation of bcl-2 resulting from a chromosomal translocation (t[14;18]) then acts to confer a survival benefit to otherwise dying cells and promotes malignant transformation.
Upregulation of the cell cycle results from inappropriate activation of the protein coded by c-Myc, a transcription factor that drives cell proliferation.
TP53 is a cell cycle inhibitor in response to the detection of a DNA error. If repair is not possible, the gene p53 then initiates apoptosis. A mutation in p53 is found in numerous cancers, including colon cancer and B-lymphocyte lymphoma.
Agonism of apoptosis is carried out by BAX, BAK, and other proapoptotic proteins. When repair of DNA is not possible, these proteins allow the release of caspase-activating proteins from the mitochondria to trigger cell death.
Constitutive activation of G proteins, such as the RAS protein, is seen in many cancers. Activation of RAS is seen in neurofibromatosis.
Inactivation of p53 occurs in a number of cancers. p53 functions as a tumor suppressor gene, so loss of p53 confers a cellular state that supports progression to malignancy.