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

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 lymphoblas...

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Main Authors: Reiter, Andreas (Author) , Walz, Christoph (Author) , Watmore, Ann (Author) , Schoch, Claudia (Author) , Blau, Ilona (Author) , Schlegelberger, Brigitte (Author) , Berger, Ute (Author) , Telford, Nick (Author) , Aruliah, Shilani (Author) , Yin, John A. (Author) , Vanstraelen, Danny (Author) , Barker, Helen F. (Author) , Taylor, Peter C. (Author) , O'Driscoll, Aisling (Author) , Benedetti, Fabio (Author) , Rudolph, Cornelia (Author) , Kolb, Hans-Jochem (Author) , Hochhaus, Andreas (Author) , Hehlmann, Rüdiger (Author) , Chase, Andrew (Author) , Cross, Nicholas C.P. (Author)
Format: Article (Journal)
Language:English
Published: April 1, 2005
In: Cancer research
Year: 2005, Volume: 65, Issue: 7, Pages: 2662-2667
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-04-4263
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/0008-5472.CAN-04-4263
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Author Notes: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, and Nicholas C.P. Cross

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520 |a 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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