The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74917
Title:
The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.
Authors:
Reiter, Andreas; Walz, Christoph; Watmore, Ann; Schoch, Claudia; Blau, Ilona; Schlegelberger, Brigitte; Berger, Ute; Telford, Nicholas; Aruliah, Shilani; Yin, John A; Vanstraelen, Danny; Barker, Helen F; Taylor, Peter C; O'Driscoll, Aisling; Benedetti, Fabio; Rudolph, Cornelia; Kolb, Hans-Jochem; Hochhaus, Andreas; Hehlmann, Rüdiger; Chase, Andrew; Cross, Nicholas C P
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.
Affiliation:
III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany. andreas.reiter@med3.ma.uni-heidelberg.de
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.
Journal:
Cancer Research
Issue Date:
1-Apr-2005
URI:
http://hdl.handle.net/10541/74917
DOI:
10.1158/0008-5472.CAN-04-4263
PubMed ID:
15805263
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorReiter, Andreas-
dc.contributor.authorWalz, Christoph-
dc.contributor.authorWatmore, Ann-
dc.contributor.authorSchoch, Claudia-
dc.contributor.authorBlau, Ilona-
dc.contributor.authorSchlegelberger, Brigitte-
dc.contributor.authorBerger, Ute-
dc.contributor.authorTelford, Nicholas-
dc.contributor.authorAruliah, Shilani-
dc.contributor.authorYin, John A-
dc.contributor.authorVanstraelen, Danny-
dc.contributor.authorBarker, Helen F-
dc.contributor.authorTaylor, Peter C-
dc.contributor.authorO'Driscoll, Aisling-
dc.contributor.authorBenedetti, Fabio-
dc.contributor.authorRudolph, Cornelia-
dc.contributor.authorKolb, Hans-Jochem-
dc.contributor.authorHochhaus, Andreas-
dc.contributor.authorHehlmann, Rüdiger-
dc.contributor.authorChase, Andrew-
dc.contributor.authorCross, Nicholas C P-
dc.date.accessioned2009-07-22T10:07:54Z-
dc.date.available2009-07-22T10:07:54Z-
dc.date.issued2005-04-01-
dc.identifier.citationThe 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.issn0008-5472-
dc.identifier.pmid15805263-
dc.identifier.doi10.1158/0008-5472.CAN-04-4263-
dc.identifier.urihttp://hdl.handle.net/10541/74917-
dc.description.abstractWe 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.en
dc.language.isoenen
dc.subjectLeukaemiaen
dc.subject.meshAcute Disease-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAutoantigens-
dc.subject.meshBase Sequence-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshChromosomes, Human, Pair 8-
dc.subject.meshChromosomes, Human, Pair 9-
dc.subject.meshHumans-
dc.subject.meshJanus Kinase 2-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshLeukemia, Myeloid-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshProtein-Tyrosine Kinases-
dc.subject.meshProto-Oncogene Proteins-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTranslocation, Genetic-
dc.titleThe t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.en
dc.typeArticleen
dc.contributor.departmentIII. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany. andreas.reiter@med3.ma.uni-heidelberg.deen
dc.identifier.journalCancer Researchen

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