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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.
AuthorsAndreas Reiter, Christoph Walz, Ann Watmore, Claudia Schoch, Ilona Blau, Brigitte Schlegelberger, Ute Berger, Nick Telford, Shilani Aruliah, John A Yin, Danny Vanstraelen, Helen F Barker, Peter C Taylor, Aisling O'Driscoll, Fabio Benedetti, Cornelia Rudolph, Hans-Jochem Kolb, Andreas Hochhaus, Rüdiger Hehlmann, Andrew Chase, Nicholas C P Cross
JournalCancer research (Cancer Res) Vol. 65 Issue 7 Pg. 2662-7 (Apr 01 2005) ISSN: 0008-5472 [Print] United States
PMID15805263 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantigens
  • Cell Cycle Proteins
  • Oncogene Proteins, Fusion
  • PCM1 protein, human
  • PCM1-JAK2 fusion protein, human
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2
Topics
  • Acute Disease
  • Adult
  • Aged
  • Amino Acid Sequence
  • Autoantigens
  • Base Sequence
  • Cell Cycle Proteins (genetics)
  • Chromosomes, Human, Pair 8 (genetics)
  • Chromosomes, Human, Pair 9 (genetics)
  • Humans
  • Janus Kinase 2
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics)
  • Leukemia, Myeloid (genetics)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion (genetics)
  • Protein-Tyrosine Kinases (genetics)
  • Proto-Oncogene Proteins (genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic

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