title: Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus.
abstract: Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor alpha locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor alpha gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RAR alpha mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor alpha gene plays a crucial role in the leukemogenesis of APL.
authors.affiliation: Istituto di Clinica Medica I, University of Perugia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Alcalay
authors.forename: D
authors.initials: D
authors.lastname: Zangrilli
authors.forename: P P
authors.initials: PP
authors.lastname: Pandolfi
authors.forename: L
authors.initials: L
authors.lastname: Longo
authors.forename: A
authors.initials: A
authors.lastname: Mencarelli
authors.forename: A
authors.initials: A
authors.lastname: Giacomucci
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.forename: F
authors.initials: F
authors.lastname: Lo Coco
mesh_terms: D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015698:Genomic Library; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism; D008168:Lung; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D014212:Tretinoin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004273:DNA, Neoplasm; D018168:Receptors, Retinoic Acid; D014212:Tretinoin