title: ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements.
abstract: Rearrangements of the ALL-1 gene by reciprocal translocations involving chromosome band 11q23 are frequently associated with human acute leukemia. We have previously reported the detection of ALL-1 gene rearrangements in adult patients with acute myeloid leukemia lacking cytogenetic evidence of 11q23 translocations. These included 2 of 19 patients with normal karyotypes as well as 3 of 4 patients with trisomy 11 as a sole cytogenetic abnormality. Rearrangement of the ALL-1 genes in two of the patients with trisomy 11 was shown to result from a direct tandem duplication of a portion of the gene spanning exons 2-6. Here we report the characterization of the ALL-1 gene rearrangement in one of the previously reported acute myeloid leukemia patients with a normal karyotype. ALL-1 rearrangement in this patient results from a direct tandem duplication of a portion of the gene spanning exons 2-8. RNA polymerase chain reaction and DNA sequence analysis show that the partially duplicated ALL-1 gene is transcribed into mRNA capable of encoding a partially duplicated protein. Sequence analysis of the genomic fusion region provides evidence for Alu-mediated homologous recombination as a mechanism for partial duplication of the ALL-1 gene.
authors.affiliation: Jefferson Cancer Institute, Jefferson Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: S A
authors.initials: SA
authors.lastname: Schichman
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: M P
authors.initials: MP
authors.lastname: Strout
authors.forename: S L
authors.initials: SL
authors.lastname: Carter
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: E
authors.initials: E
authors.lastname: Canaani
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11; D005091:Exons / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*