title: A new variant translocation in acute promyelocytic leukaemia: molecular characterization and clinical correlation.
abstract: Translocation t(15;17)(q22;q21) is an acquired clonal cytogenetic change present in almost all cases of acute promelocytic leukemia (APL). The molecular genetic basis of the translocation supports its integral role in pathogenesis. We describe a patient with APL in whom the leukaemic clone was characterized by a true variant of the classical t(15;17). The patient whose disease had numerous atypical clinical features, had t(11;17)(q13;121). The chromosome 17 breakpoint was localized to intron 2 of RARA by Southern blotting, and there was no evidence at the molecular level for rearrangement at PML locus. These data, along with previous reports of rare variant translocations in APL, indicate that while dysregulation of RARA by gene fusion may be essential for the APL phenotype, the particular fusion partner may determine clinicopathological aspects, including presentation, response to treatment with all-trans retinoic acid (ATRA), and prognosis. This heterogeneity suggests that the variant fusion partners of RARA in APL encode factors with properties both common to and distinct from those of PML. Investigation of these factors promises to shed light on the complex development pathways involved in the regulation of haematopoiesis.
authors.affiliation: Division of Haemotology, University of Toronto, ON, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Wells
authors.forename: J L
authors.initials: JL
authors.lastname: Hummel
authors.forename: A
authors.initials: A
authors.lastname: De Koven
authors.forename: A
authors.initials: A
authors.lastname: Zipursky
authors.forename: M
authors.initials: M
authors.lastname: Kirby
authors.forename: I
authors.initials: I
authors.lastname: Dubé
authors.forename: S
authors.initials: S
authors.lastname: Kamel-Reid
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D007223:Infant; D007438:Introns; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011379:Prognosis; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D015183:Restriction Mapping; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin