THE BCR GENE RECOMBINES PREFERENTIALLY WITH ALU ELEMENTS IN COMPLEX BCR-ABL TRANSLOCATIONS OF CHRONIC MYELOID-LEUKEMIA

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromo some 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL ge ne with leukaemogenic properties. The mechanism which underlies this r ecombination is unknown, but additional chromosome sites may be involv ed to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. He re, we show that the 3' part of M-Bcr recombined within, or immediatel y adjacent to, Alu elements at the additional sites in all five comple x BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BC R-ABL recombination process in complex rearrangements, and provides ad ditional evidence for the association of these elements with somatic r earrangements which cause human leukaemia. We further show that sequen ce motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensu s. Expressed sequences mapped close to the breakpoint sites on other c hromosomes in three of the five cases examined.