The bcl-2 gene is overexpressed in 80% to 90% of patients with follicular NHL. The product of this gene, the bcl-2 protein, not only protects cells from apoptosis but also induces a form of acquired resistance to a wide array of chemotherapy agents (Kitada et al: Blood 91:3379-3389, 1998).
In vitro studies by Alas et al (abstract #2479) suggest that rituximab(Drug information on rituximab) down-regulates bcl-2 expression and upregulates factors that induce cell-cycle arrest. These observations support the hypothesis that rituximab can sensitize lymphoma cells in vitro to chemotherapeutic agents. Such in vitro studies may provide the rationale for various antibody/chemotherapy combinations.
Bruce D. Cheson, MD