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

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 7; pp. 2662 - 2667
• Main Authors: REITER, Andreas, WALZ, Christoph, VANSTRAELEN, Danny, BARKER, Helen F, TAYLOR, Peter C, O'DRISCOLL, Aisling, BENEDETTI, Fabio, RUDOLPH, Cornelia, KOLB, Hans-Jochem, HOCHHAUS, Andreas, HEHLMANN, Rudiger, CHASE, Andrew, WATMORE, Ann, CROSS, Nicholas C. P, SCHOCH, Claudia, BLAU, Ilona, SCHLEGELBERGER, Brigitte, BERGER, Ute, TELFORD, Nick, ARULIAH, Shilani, YIN, John A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-04-2005
• Subjects: Acute Disease; Adult; Aged; Amino Acid Sequence; Antineoplastic agents; Autoantigens; Base Sequence; Biological and medical sciences; 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; Medical sciences; Middle Aged; Molecular Sequence Data; Oncogene Proteins, Fusion - genetics; Pharmacology. Drug treatments; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; Translocation, Genetic; Chronic; Relapse; Enzyme; Toxicity; Transferases; Acute leukemia; Protein-tyrosine kinase; Jak 2 protein kinase
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-04-4263

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.