Follicular lymphoma, Bcl-2, and cell growth

Follicular lymphoma is a blood cancer where B-cells have an unusually long lifespan, much longer than that of normal B-cells, which can be as short as a few days and as long as two months. These longer-living B-cells cluster in the lymph nodes and clog the lymphatic system. Through karyotyping, which lines up all the chromosomes and compares homologous chromosomes, scientists have observed that chromosomes 14 and 18 appear different in the longer-living B-cells than they do in normal B-cells. They concluded that there was a translocation between chromosome 14 and 18. It has also been observed that these B-cells with translocations express a protein identified as bcl-2 in excess. Follicular lymphoma is a slow progressing cancer, and the B-cells inside an individual with follicular lymphoma do not divide any faster than normal B-cells.

It was hypothesized that the over-expression of bcl-2 might be related to the extended lifespan of these B-cells. Normally B-cells are terminated by apoptosis which is not observed or triggered as quickly in these longer-living B-cells. To test this, researchers created an antisense phosphorothioate (PS) oligodeoxynucleotide of the bcl-2 gene and observed cell density over time when this antisense PS oligodeoxynucleotide was introduced to colonies of B-cells that express bcl-2 in excess. A phosphorothioate oligodeoxynucleotide is similar to a phosphodiester oligodeoxynucleotide except an oxygen atom has been replaced by a sulfur atom (see Figure 1).

To make sure the results from the antisense PS nucleotide experiment were accurate, the researchers also observed colonies of B-cells exposed to a bcl-2 PS sense strand and colonies of B-cells exposed to saline solution. The results are shown in Figure 2.