Ph1+bcr- acute leukemias: implication of Alu sequences in a chromosomal translocation occurring in the new cluster region within the BCR gene.
Chromosomal breakpoints on chromosome 22 are located in the first intron of the bcr gene in half of the Philadelphia-positive acute leukemias (Ph1+bcr- AL). We have previously shown that, in these cases, the breakpoints are clustered in the 3' portion of the bcr gene first intron, particularly in a region called bcr2 or m-bcr-1. In order to search for mechanisms underlying the reciprocal chromosome translocation, molecular analysis of breakpoints on chromosome 9 and 22 were performed in a Ph1+bcr- acute lymphoblastic leukemia with bcr2 rearrangement. The comparison of rearranged sequences with their normal counterparts showed that human repetitive Alu sequences were physically linked to the translocation on both chromosomes. In addition an inverted Alu repeat was found 5' to each rearranged Alu sequence on chromosome 22 and 9, with an intervening sequence of 210 and 90bp respectively. This allows to propose a new model, still to be confirmed, of recombination after formation of two hairpin structures which could facilitate the genesis of the chromosomal accident.
Chen
S J
SJ
Unité INSERM U301, Hôpital Saint-Louis, Paris, France.
Chen
Z
Z
d'Auriol
L
L
Le Coniat
M
M
Grausz
D
D
Berger
R
R
D000208:Acute Disease; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr; D011519:Proto-Oncogenes; D012091:Repetitive Sequences, Nucleic Acid; D014178:Translocation, Genetic
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr