Cancer: Follicular lymphoma and bcl-2

Follicular lymphoma is a slow progressing cancer that involves the clustering of B cells in the lymph nodes. B cells in an individual with follicular lymphoma do not divide much faster than normal B cells; however, they have an unusually long lifespan – much longer than that of normal B cells. Scientists believe this extended lifespan involves changes in chromosomes 14 and 18, which appear differently in the longer-living B cells than they do in normal B cells. In many cases of follicular lymphoma, there is a translocation between chromosomes 14 and 18, which leads to excess expression of the bcl-2 protein. Scientists hypothesize that the over-expression of bcl-2 might be related to the extended lifespan of these B cells.

Researchers testing this hypothesis created sense and antisense phosphorothioate (PS) oligodeoxynucleotides of the bcl-2 gene. A PS oligodeoxynucleotide is similar to a phosphodiester oligodeoxynucleotide (i.e. DNA), except that an oxygen atom in the backbone has been replaced by a sulfur atom (Figure 1), which increases the stability of the molecule. The researchers observed cell density over time when the PS oligodeoxynucleotides were introduced to colonies of B cells that expressed bcl-2 in excess. The results are shown in Figure 2.

Figure 1 Structure of a PS oligodeoxynucleotide

Figure 2 Cell density versus time in experimental and control groups