AbstractWe performed molecular cloning and sequencing of the breakpoints of a new chromosomal translocation involving theMYCprotooncogene locus. This secondary t(8; 12)(q24;q22) was associated with a primary t( I I; 14)(q I 3;q32) translocation in a case of B‐cell chronic lymphocytic leukemia (CLL) in blastic transformation. In this leukemia, Northern blot and nuclease analyses SI showed thatMYCwas strongly expressed with initiation of the transcription at both the 5′ and 3′ promoters as observed in Burkitt's lymphomas; no coding change was observed inMYCputative regulatory sequences. The breakpoint on chromosome 8 mapped to the 3′ end of theMYClocus, in a region containing a potential Z‐DNA tract, and where we identified two DNase I hypersensitive sites. A rearrangedMYCgene fragment was cloned and shown to contain chromosome 12 information by Southern blot analysis and by in situ hybridization. A genomic probe subcloned from the isolated region of the chromosome 12 recognized a 1.8 kb transcript in virtually all the tissues tested but a preferential expression of this new gene, which we termedBTGI(for B‐cell translocation gene I) was observed in the CLL cells and in tissues of lymphoid origin. This chromosome 12 coding sequence is conserved in evolution and a transcript of similar size is present in mur