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.
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Authors | Andreas 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 |
Journal | Cancer research
(Cancer Res)
Vol. 65
Issue 7
Pg. 2662-7
(Apr 01 2005)
ISSN: 0008-5472 [Print] United States |
PMID | 15805263
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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