Analysis of a regulatory element in the 5'-untranslated region of the bcl-2 gene

The bcl-2 gene is an important antagonist of apoptosis, the programmed cell death. Bcl-2 is highly expressed in a variety of lymphomas. Lymphocytes of patients with chronic lymphocytic leukemia (CLL) express high amounts of bcl-2 even in the absence of the t(14;18) translocation, resulting in a strong resistance towards corticosteroid induced apoptosis. Within the 5'-untranslated region of the bcl-2 gene a p53 dependent negative response element has been described. Genetic alterations within this element could lead to uncontrolled overexpression of bcl-2 and subsequent resistance towards apoptosis. We therefore analyzed the mRNA from the 5'-untranslated region -279 to -85 bp of the bcl-2 gene by direct PCR sequencing from peripheral blood derived lymphocytes from patients with CLL and normal healthy donors. Compared to published sequences (Tsujimoto and Croce (1986) Proc. Natl. Acad. Sci. USA 83, 5214), we consistently found an exchange at position 1271 from A to G and at position 1284 from G to A in all CLL as well as normal donor derived samples analyzed. Thus, CLL specific alterations compared to normal cells could not be found and deregulated expression of bcl-2 in CLL cells does not appear to be due to alterations in the p53 dependent negative response element of the bcl-2 gene. However, our data add information to published sequence data of this region.