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In March 2006 a 57-year-old male was admitted to hospital, complaining of a short period of asthenia and night sweats. Laboratory analysis demonstrated markedly elevated leukocytes (37 ! 10 9 /l) with 87% of blasts, hemoglobin of 10.4 g/dl and thrombocytopenia of 43 ! 10 9 /l. Subsequent bone marrow investigation revealed dominant leukemic infiltration (90%) composed of myeloid blasts without maturation, consistent with the diagnosis of AML not otherwise categorized (according to WHO 2008), morphologically type AML without maturation. Cytogenetics as well as molecular analysis remained unremarkable, giving no evidence of recurrent genetic abnormalities. The patient was treated on HOVON 42 Protocol Arm A receiving 2 cycles of induction chemotherapy with cytarabine/idarubicin and cytarabine/amsacrine, respectively, which resulted in early first complete remission. According to the protocol and due to the lack of an appropriate donor for allogeneic hematopoietic stem cell transplantation, therapy was completed with consolidation chemotherapy with mitoxantrone/etoposide. Four years later, in June 2010, a slight thrombocytosis was first noted and increased in time to 717 ! 10 9 /l in June 2011, with otherwise normal full blood count values. Peripheral blood analysis for the JAK2 V617F mutation was positive (allele burden 34%). The red cell mass as well as the EPO level was in the normal range, and bone marMyeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by increased proliferation of one to three hematopoietic cell lineages. The protein tyrosine kinase JAK2 is mutated in virtually all patients with polycythemia vera and approximately 60% of patients with primary myelofibrosis or essential thrombocythemia [1] . In the past years less prevalent mutations involving MPL, TET2, ASXL1, CBL, IDH1 and IDH2, EZH2, DNMT3A as well as IKZF1 have additionally been described [2] . The transformation of MPN in acute myeloid leukemia (AML) is a well-reported phenomenon. However, how JAK2 and other MPN-associated mutations contribute to disease progression is still the subject of debate [2–4] . In contrast, JAK2-positive MPN as secondary neoplasia occurring after AML is a rare clinical observation with only few case reports in the literature [5, 6] and little is known about the underlying pathophysiology. Here we report the unique case of a 62-year-old patient with secondary MPN harboring JAK2 V617F, which presented with isolated thrombocytosis 4 years after successful treatment with chemotherapy of a JAK2-negative AML. The idea that the expansion of the JAK2 V617F clone is associated with AML-linked factors is supported by the fact that our patient had a third malignancy, pancreatic cancer, associated with dysregulation in JAK/ STAT3 signaling. Received: June 18, 2012 Accepted: July 1, 2012 Published online: September 19, 2012

JAK2 V617F-Mutated Myeloproliferative Neoplasia Developing Five Years after Wild-Type JAK2 Acute Myeloid Leukemia: A Case Report