title: Molecular cloning of a 5' segment of the genomic phl gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemias.
abstract: Molecular rearrangements of Ph1 chromosome, the hallmark of CML, are clustered in a 5.8-kb DNA segment, the so-called breakpoint cluster region (bcr) of the phl gene that is localized to chromosome 22q11. In Ph1-positive (Ph1+) ALLs, the rearrangements have been shown to involve either the 5.8-kb bcr (called bcr+) or a region upstream of bcr in the 5' end of the phl gene (bcr-). To gain insight into the rearrangements occurring in Ph1+ acute leukemias, a 64-kb DNA fragment from the 5' end of phl was analyzed in order to generate molecular probes covering 40 kb of the phl gene first intron. A panel of seven cases of bcr-Ph1+ acute leukemia (three nonlymphocytic and four lymphocytic) was investigated with these intron 1-derived probes. Strikingly, in six of the seven leukemias, the breakpoints were located in a 10.8-kb DNA segment, defining a new bcr which appears to be specific for Ph1+ acute leukemias. By analogy with the CML bcr region located in the 3' part of the phl gene, we propose to designate this 10.8-kb fragment bcr2.
authors.affiliation: INSERM U301, Centre Hayem, Hôpital Saint-Louis, Paris, France.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: J D
authors.initials: JD
authors.lastname: Grausz
authors.forename: J
authors.initials: J
authors.lastname: Hillion
authors.forename: L
authors.initials: L
authors.lastname: d'Auriol
authors.forename: G
authors.initials: G
authors.lastname: Flandrin
authors.forename: C J
authors.initials: CJ
authors.lastname: Larsen
authors.forename: R
authors.initials: R
authors.lastname: Berger
mesh_terms: D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009857:Oncogenes; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011995:Recombination, Genetic; D015183:Restriction Mapping