Structural alterations of the BCR and ABL genes in Ph1 positive acute leukemias with rearrangements in the BCR gene first intron: further evidence implicating Alu sequences in the chromosome translocation.

In the Philadelphia positive bcr negative acute leukemias (Ph1+bcr- AL), the chromosomal breakpoints on chromosome 22 have been shown clustered within 10.8kb (bcr2) and 5kb (bcr3) fragments of the first intron of the BCR gene. We previously reported that the breakpoints were localized in Alu repeats on chromosomes 9 and 22 in a Ph1+bcr- acute lymphoblastic leukemia with a rearrangement involving bcr2. Molecular data of two other Ph1 translocations, one a Ph1+bcr- acute myeloblastic leukemia in the bcr2 region, and the other an acute lymphoblastic leukemia in the bcr3 region are presented. In the former, the breakpoints on chromosomes 9 and 22 are localized in Alu repeats, in regions with two inverted Alu sequences, as in our previously reported case. In the second leukemia, the breakpoints are not located in Alu sequences, but such repeats are found in their vicinity. The implications of these findings are discussed.