26The JAK2V617F point mutation has been implicated in the pathogenesis of the vast majority of 27 myeloproliferative neoplasms (MPNs), but translocations involving JAK2 have increasingly been 28 identified in a subset of patients with JAK2V617F-negative MPNs. Here we present a case of a patient 29 diagnosed with JAK2V617F-negative polycythemia vera (PV) that transformed to MPN-blast phase 30 (MPN-BP). Cytogenetic and FISH analysis revealed a novel translocation of t(1;9)(p36;p24.1) and a 31 PEX14-JAK2 gene fusion, as a result of the translocation, was identified. The t(1;9)(p36;p24.1) has not 32 been previously described and represents a new addition to the list of known translocations involving 33 JAK2 that have been identified in hematologic malignancies. Although the prognostic and treatment 34 implications of JAK2 translocations in MPNs is not yet clear, positive outcomes have been described in 35 early case reports of the use of JAK inhibitors in these patients. Further research into the role of JAK2 36 translocations in the pathogenesis and outcomes of hematologic malignancies is warranted.
53the MPNs, but have also been identified in de novo leukemias of both myeloid and lymphoid lineages 54 (Table 2).
56Here we describe a case of a patient with JAK2V617F-negative PV who was found to have a novel JAK2 57 translocation, not previously described. We also provide a review of the known JAK2 translocations 58 associated with PV and other MPNs.59 4 60 Case Report 61 A 52 year old woman initially presented in 2008 with symptoms of headaches, dizziness, fatigue, 62 shortness of breath and numbness and tingling of the hands and feet and was found to have a 63 hematocrit (HCT) of 61% with normal white blood count (WBC) and platelet (PLT) count. The bone 64 marrow biopsy showed a hypercellular marrow (95%) with increased megakaryocytes in clusters, 65 without reticulin staining. The patient was found to meet World Health Organization's (WHO) diagnostic 66 criteria for JAK2V617F mutation negative PV and was initiated on treatment with aspirin and therapeutic 67 phlebotomy, to maintain the Hct <42%.68 69 A year later, the patient developed leukocytosis with a WBC 30 x10 9 /L and thrombocytosis with a PLT 70 count of 600,000/L. She was started on hydroxyurea at a dose of 500 mg daily, with subsequent 71 improvement in leukocytosis and thrombocytosis, but developed treatment emergent anemia. Repeat
72bone marrow biopsy and aspirate at that time showed a hypercellular marrow (100%) with trilineage 73 hematopoiesis, marked granulocytic hyperplasia, increased immature forms, with markedly increased 74 eosinophils (31%) and 7% blasts. Peripheral blood flow cytometry showed a small CD33+ and CD34+ 75 myeloblast population (1.4%).
77Several months following initiation of hydroxyurea, the patient developed constitutional symptoms. The
78WBC was found to be elevated to 72x 10 9 /L and peripheral blasts were 21%, consistent with 157 158 Translocations at 9p24.1 and the resultant gene fusion products have been identified ...