title: The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.
abstract: We have identified a t(8;9)(p21-23;p23-24) in seven male patients (mean age 50, range 32-74) with diverse hematologic malignancies and clinical outcomes: atypical chronic myeloid leukemia/chronic eosinophilic leukemia (n = 5), secondary acute myeloid leukemia (n = 1), and pre-B-cell acute lymphoblastic leukemia (n = 1). Initial fluorescence in situ hybridization studies of one patient indicated that the nonreceptor tyrosine kinase Janus-activated kinase 2 (JAK2) at 9p24 was disrupted. Rapid amplification of cDNA ends-PCR identified the 8p22 partner gene as human autoantigen pericentriolar material (PCM1), a gene encoding a large centrosomal protein with multiple coiled-coil domains. Reverse transcription-PCR and fluorescence in situ hybridization confirmed the fusion in this case and also identified PCM1-JAK2 in the six other t(8;9) patients. The breakpoints were variable in both genes, but in all cases the chimeric mRNA is predicted to encode a protein that retains several of the predicted coiled-coil domains from PCM1 and the entire tyrosine kinase domain of JAK2. Reciprocal JAK2-PCM1 mRNA was not detected in any patient. We conclude that human autoantigen pericentriolar material (PCM1)-JAK2 is a novel, recurrent fusion gene in hematologic malignancies. Patients with PCM1-JAK2 disease are attractive candidates for targeted signal transduction therapy.
authors.affiliation: III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany. andreas.reiter@med3.ma.uni-heidelberg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Christoph
authors.initials: C
authors.lastname: Walz
authors.forename: Ann
authors.initials: A
authors.lastname: Watmore
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Ilona
authors.initials: I
authors.lastname: Blau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Ute
authors.initials: U
authors.lastname: Berger
authors.forename: Nick
authors.initials: N
authors.lastname: Telford
authors.forename: Shilani
authors.initials: S
authors.lastname: Aruliah
authors.forename: John A
authors.initials: JA
authors.lastname: Yin
authors.forename: Danny
authors.initials: D
authors.lastname: Vanstraelen
authors.forename: Helen F
authors.initials: HF
authors.lastname: Barker
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Driscoll
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rudolph
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Andrew
authors.initials: A
authors.lastname: Chase
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001324:Autoantigens; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; D015514:Oncogene Proteins, Fusion; C086074:PCM1 protein, human; C575876:PCM1-JAK2 fusion protein, human; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2