title: The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.
abstract: We have studied an acute promyelocytic leukemia (APL) patient with a variant t(5;17)(q32;q12). This translocation fuses the gene for the nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA). Two alternatively spliced transcripts are expressed, which differ in 129 bases immediately upstream of the RARA sequence. The NPM sequences contained in the shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK fusion gene expressed in t(2;5) lymphomas. The RARA sequences are the same as the RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL, respectively. Both NPM-RAR transcripts fuse NPM and RARA sequence in the same reading frame, to generate translation products of 57 kD and 62 kD. Both NPM-RAR proteins are expressed in the patient's leukemic cells, along with wild-type RARA derived from the uninvolved allele. In transcriptional assays using a retinoic acid response element reporter construct, both NPM-RAR fusion proteins act as retinoic acid-dependent transcriptional activators. This case defines a third class of APL rearrangements, all of which generate fusion proteins of RARA.
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, PA 15213, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Redner
authors.forename: E A
authors.initials: EA
authors.lastname: Rush
authors.forename: S
authors.initials: S
authors.lastname: Faas
authors.forename: W A
authors.initials: WA
authors.lastname: Rudert
authors.forename: S J
authors.initials: SJ
authors.lastname: Corey
mesh_terms: D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure*; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D056489:Nucleoplasmins; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D010750:Phosphoproteins; D012326:RNA Splicing; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; C000607071:RARA protein, human; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D015534:Trans-Activators; D014212:Tretinoin