IDENTIFICATION OF BCD A NOVEL PROTOONCOGENE EXPRESSED IN B-CELLS

A novel B-cell derived (Bcd) oncogene has been isolated from the perip heral blood lymphocytes of one B-cell chronic lymphocytic leukemia (B- CLL) patient using DNA transfer and a mouse tumorigenicity assay. The Bcd proto-oncogene was activated by a truncation in the 5' UTR, It pre dicts for two open reading frames (ORFs). ORF1 consists of 240 bp that would encode 80 amino acids, while the major ORF2 consists of 648 bp capable of coding for 216 amino acids, Predicted peptide sequence of O RF2 contained a zinc finger domain which showed significant homology t o GC box binding proteins BTEB2 and SP1. Transfection of an expression vector containing ORF2 but not full length cDNA was able to transform NIH3T3 cells and induce tumors in nude mice. Bcd mRNA transcripts of less than or equal to 2.6 kb were selectively expressed in PBL and tes tis of healthy individuals. Within the PBL, Bcd gene expression was re stricted to CD19(+) B-cells and absent from CD14(+) monocytes and T-ce lls. Bcd transcripts were detected in all normal PBL samples tested bu t not in several malignant human B-cell lines and not in 50% of B-cell s from B-CLL patients, However, stimulation of B-cells from B-CLL pati ents under conditions which induced differentiation into plasma cells was associated with induction of Bcd gene expression, The Bcd gene may therefore play an important role in B-cell growth and development.