Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention AACR Conference on Molecular Diagnostics - 2008
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[Cancer Research 65, 2662-2667, April 1, 2005]
© 2005 American Association for Cancer Research

Molecular Biology, Pathobiology, and Genetics

The t(8;9)(p22;p24) Is a Recurrent Abnormality in Chronic and Acute Leukemia that Fuses PCM1 to JAK2

Andreas Reiter1, Christoph Walz1, Ann Watmore2, Claudia Schoch3, Ilona Blau4, Brigitte Schlegelberger5, Ute Berger1, Nick Telford6, Shilani Aruliah7, John A. Yin8, Danny Vanstraelen9, Helen F. Barker10, Peter C. Taylor10, Aisling O'Driscoll11, Fabio Benedetti12, Cornelia Rudolph5, Hans-Jochem Kolb3, Andreas Hochhaus1, Rüdiger Hehlmann1, Andrew Chase13,14 and Nicholas C.P. Cross13,14

1 III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany; 2 North Trent Cytogenetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom; 3 Labor für spezielle Leukämiediagnostik and Medizinische Klinik III, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany; 4 Hämatologisch-onkologische Schwerpunktpraxis, Berlin, Germany; 5 Medizinische Hochschule Hannover, Hannover, Germany; 6 Oncology Cytogenetics Service, Christie Hospital, Manchester, United Kingdom; 7 Cytogenetics Laboratory, Mayday University Hospital, Croydon, United Kingdom; 8 University Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom; 9 Department of Haematology and Oncology, Virga Jesse Hospital, Hasselt, Belgium; 10 Department of Haematology, Rotherham General Hospital, Rotherham, United Kingdom; 11 Department of Haematology, Worthing Hospital, Worthing, United Kingdom; 12 Centro Trapianto Midollo Osseo, Azienda Ospedaliera di Verona, Verona, Italy; 13 Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom; and 14 Human Genetics Division, University of Southampton, Southampton, United Kingdom

Requests for reprints: Andreas Reiter, M.D. III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany. Phone: 49-621-383-4115; Fax: 49-621-383-4201; E-mail: andreas.reiter{at}med3.ma.uni-heidelberg.de.

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.

Key Words: PCM1 • JAK2 • leukemia




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