Molecular genetic markers in lymphoproliferative disorders

The elucidation of the genetic mechanisms involved in the generation of antibody diversity is little more than a decade old, but the impact has already been felt in many areas of biology and medicine. In order for a B or T cell to become a functional antigen recognizing cell it must produce a unique protein to act as a membrane receptor. In the case of the B cell this is an immunoglobulin molecule while in the T cell it is an analogous dimeric protein, the T cell receptor. Diversity in these proteins is generated by a shuffling of the genes responsible for these respective proteins and is unique to each cell. Using Southern blot hybridization to exploit this, it is possible to determine whether a group of lymphocytes is derived from a single progenitor cell, i.e., clonal, and also whether they are of B or T cell origin. Oncogene activity and chromosomal translocations are believed to be responsible for a variety of lymphomas and leukemias. The association of established oncogenes, such as c-myc, with translocations to regions near immunoglobulin enhancers in some lymphomas has prompted successful searches for novel proto-oncogenes in other forms of lymphomas that also have characteristic, but different, translocations.