title: A PML/RARA chimeric gene on chromosome 12 in a patient with acute promyelocytic leukemia (M4) associated with a new variant translocation: t(12;15;17)(q24;q24;q11).
abstract: Acute promyelocytic leukemia (APL) is genetically characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17)(q22;q21), which results in the fusion gene PML-RARA. A small proportion of patients with APL have complex or simple variants of this translocation. With conventional cytogenetic methods, these translocations are detected in about 70-90 % of patients, with most of the negative results due to technical problems or cryptic variants. Those masked PML/RARA fusions can be identified by molecular analyses such as reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). We report the case of a 58-year-old man showing morphological, cytochemical, and immunophenotypic features of hypergranular APL (FAB-M4). PML-RARA transcripts were not evident on RT-PCR. Although cytogenetic tests revealed the presence of an apparently balanced translocation t(15;17)(q24;q11) with an abnormal chromosome 12 that characterized a M3 leukemia. This karyotypic interpretation was confirmed by FISH with the use of painting probes of chromosomes 12, 15, and 17 and a PML-RARA dual-color DNA probe. FISH showed a PML-RARA fusion gene on the der(12) instead of the der(15). The patient was treated with an all-trans retinoic acid (ATRA) plus anthracycline-based protocol and achieved complete remission, with no recurrence to date. These results illustrate the usefulness of combining cytogenetics and FISH methods to evidence the PML/RARA fusion gene in cases with morphologic suspicion of APL with variant or cryptic t(15;17).
authors.affiliation: Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia. aydabennour@yahoo.fr
authors.forename: Ayda
authors.initials: A
authors.lastname: Bennour
authors.forename: Ikram
authors.initials: I
authors.lastname: Tabka
authors.forename: Yosra Ben
authors.initials: YB
authors.lastname: Youssef
authors.forename: Monia
authors.initials: M
authors.lastname: Zaier
authors.forename: Sondess
authors.initials: S
authors.lastname: Hizem
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Khelif
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.forename: Halima
authors.initials: H
authors.lastname: Sennana
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein