BCL-2 REARRANGEMENT DETECTED BY PULSED-FIELD GEL-ELECTROPHORESIS (PFGE) IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) CELLS

B-chronic lymphocytic leukemia (CLL) is characterized by an accumulati on of long-lived, resting B cells expressing the Bcl-2 protein. Howeve r, less than 10% of the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional Southern blotting analysis. In the pre sent study, rearrangement of the bcl-2 gene in CLL cells was studied b y pulsed-field get electrophoresis (PFGE). With this method, large DNA fragments (> 50-10,000 kb) could be analyzed. Blood CLL cells from 9 of 9 patients and 2 of 2 CLL cell lines showed rearranged bcl-2 gene. In comparison, healthy blood B cells and lymphoblastoid cell lines (LC Ls) established from normal peripheral blood lymphocytes of the patien ts showed only germ line configuration. Thus, the possibility of restr iction fragment length polymorphisms (RFLPs) in this gene could be exc luded. The primary cell involved in CLL might be a progenitor B cell t hat has accidentally rearranged the bcl-2 gene. As a consequence, such cells express stable amount of Bcl-2 protein and do not enter apoptos is. During prolonged survival, such cells may acquire secondary change s including chromosomal translocations and mutations.