title: Submicroscopic insertion of RARalpha gene into chromosome 15 in two cases of acute promyelocytic leukemia.
abstract: Acute promyelocytic leukemia (APL) is characterized by a specific translocation (15;17)(q22;q21), resulting in the formation of PML/RARalpha chimeric transcripts. We report two female patients with PML/RARalpha-positive classical APL, whose leukemic cells expressed a variant translocation, t(5;15)(q13;q22) and t(15;17)(q22;p13), respectively. Both translocations were confirmed by whole chromosome painting which revealed no apparent involvement of 17q. A two-color fluorescence in situ hybridization with a 5' PML and a 3' RARalpha probe showed, in both cases, the presence of a PML-RARalpha fusion gene, on the der(15)t(5;15) long arm, and on the der(17)t(15;17) short arm, respectively. These two complex rearrangements resulted most probably from a two-step mechanism: (1) a submicroscopic insertion into 15q of a 17q segment including the 3' part of the RARalpha gene; (2) a reciprocal translocation between der(15) and a variable chromosome arm, with a breakpoint distal and proximal to RARalpha insertion in the case of t(5;15) and t(15;17), respectively. Molecular and prognosis significance of these variant translocations are discussed.
authors.affiliation: Département d'Hématologie, Laboratoire de Cytogénétique, Hôpital Hôtel-Dieu, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Viguié
authors.forename: A
authors.initials: A
authors.lastname: Aboura
authors.forename: S
authors.initials: S
authors.lastname: Ramond
authors.forename: D
authors.initials: D
authors.lastname: Bouscary
authors.forename: M
authors.initials: M
authors.lastname: Baudard
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
authors.forename: J P
authors.initials: JP
authors.lastname: Marie
mesh_terms: D000368:Aged; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics* / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics* / Q000648:ultrastructure; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein