PCM1-JAK2-fusion: a potential treatment target in myelodysplastic-myeloproliferative and other hemato-lymphoid neoplasms.

IMPORTANCE OF THE FIELD: Activating mutations of the JAK2 gene are of tumorigenic significance in myeloproliferative neoplasms. Translocations involving the JAK2 locus are of oncogenic importance in acute leukemias, myelodysplastic/myeloproliferative diseases and T-cell lymphomas. JAK2 locus gains, which are recurrent in Hodgkin's- and primary mediastinal B-cell lymphoma, are also efficient mechanisms of JAK2 activation. Recently, specific drugs blocking JAK2 have been developed and are currently in clinical trials. AREAS COVERED IN THIS REVIEW: We discuss possible mechanisms of deregulation and the significance of pericentriolar material 1 (PCM)1-JAK2 fusion/t(8;9)(p21-23;p23-24) in hematolymphoid neoplasms. Such cases show morphological (myeloproliferaton, eosinophilia, myelofibrosis) and clinical (striking male predominance, aggressive course) similarities. Since increased JAK2 oligomerization and tyrosine kinase domain activation is the probable oncogenic mechanism in this instance, such patients are promising candidates for JAK2 inhibitor therapy. WHAT THE READER WILL GAIN: The reader will gain important insights considering PCM1-JAK2 fusion in hematologic malignancies. TAKE HOME MESSAGE: JAK2 is a tyrosine kinase with oncogenic potential in hematologic malignancies. It can be activated by point mutations, translocations and amplifications. Beyond malignancies associated with JAK2 point mutations, those associated with translocations might be suitable for tyrosine kinase inhibitors, which merits prospective evaluation.