The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.
dc.contributor.author | Reiter, Andreas | |
dc.contributor.author | Walz, Christoph | |
dc.contributor.author | Watmore, Ann | |
dc.contributor.author | Schoch, Claudia | |
dc.contributor.author | Blau, Ilona | |
dc.contributor.author | Schlegelberger, Brigitte | |
dc.contributor.author | Berger, Ute | |
dc.contributor.author | Telford, Nicholas | |
dc.contributor.author | Aruliah, Shilani | |
dc.contributor.author | Yin, John A | |
dc.contributor.author | Vanstraelen, Danny | |
dc.contributor.author | Barker, Helen F | |
dc.contributor.author | Taylor, Peter C | |
dc.contributor.author | O'Driscoll, Aisling | |
dc.contributor.author | Benedetti, Fabio | |
dc.contributor.author | Rudolph, Cornelia | |
dc.contributor.author | Kolb, Hans-Jochem | |
dc.contributor.author | Hochhaus, Andreas | |
dc.contributor.author | Hehlmann, Rüdiger | |
dc.contributor.author | Chase, Andrew | |
dc.contributor.author | Cross, Nicholas C P | |
dc.date.accessioned | 2009-07-22T10:07:54Z | |
dc.date.available | 2009-07-22T10:07:54Z | |
dc.date.issued | 2005-04-01 | |
dc.identifier.citation | The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. 2005, 65 (7):2662-7 Cancer Res. | en |
dc.identifier.issn | 0008-5472 | |
dc.identifier.pmid | 15805263 | |
dc.identifier.doi | 10.1158/0008-5472.CAN-04-4263 | |
dc.identifier.uri | http://hdl.handle.net/10541/74917 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Leukaemia | en |
dc.subject.mesh | Acute Disease | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Amino Acid Sequence | |
dc.subject.mesh | Autoantigens | |
dc.subject.mesh | Base Sequence | |
dc.subject.mesh | Cell Cycle Proteins | |
dc.subject.mesh | Chromosomes, Human, Pair 8 | |
dc.subject.mesh | Chromosomes, Human, Pair 9 | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Janus Kinase 2 | |
dc.subject.mesh | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | |
dc.subject.mesh | Leukemia, Myeloid | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Molecular Sequence Data | |
dc.subject.mesh | Oncogene Proteins, Fusion | |
dc.subject.mesh | Protein-Tyrosine Kinases | |
dc.subject.mesh | Proto-Oncogene Proteins | |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | |
dc.subject.mesh | Translocation, Genetic | |
dc.title | The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. | en |
dc.type | Article | en |
dc.contributor.department | III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany. andreas.reiter@med3.ma.uni-heidelberg.de | en |
dc.identifier.journal | Cancer Research | en |
html.description.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. |