The BCR gene recombines preferentially with Alu elements in complex BCR- ABL translocations of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome22 and ABL on chromosome 9, recombine to form a hybrid BCR- ABL gene withleukaemogenic properties. The mechanism which underlies this recombinationis unknown, but additional chromosome sites may be involved to form complexBCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' partof M-Bcr recombined within, or immediately adjacent to, Alu elements at theadditional sites in all five complex BCR-ABL rearrangements that have beenexamined so far. This is a new finding which suggests that Alu sequenceshave an affinity for the BCR-ABL recombination process in complexrearrangements, and provides additional evidence for the association ofthese elements with somatic rearrangements which cause human leukaemia. Wefurther show that sequence motifs similar to IgH switch pentamers andconsensus binding sites of the lymphoid-associated Translin protein arepresent on one or more participating strands at 3'M-Bcr recombinationsites. Motifs similar to Translin-binding sites were also identified withinthe Alu consensus. Expressed sequences mapped close to the breakpoint siteson other chromosomes in three of the five cases examined.