Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Brief Communication Acta Haematol 2013;129:23–25 DOI: 10.1159/000342100 JAK2 V617F-Mutated Myeloproliferative Neoplasia Developing Five Years after Wild-Type JAK2 Acute Myeloid Leukemia: A Case Report Sabine Girsberger a Axel Karow b Pontus Lundberg b Stephan Dirnhofer c Thomas Lehmann a Jakob R. Passweg a André Tichelli a Radek Skoda b Alicia Rovó a a Department of Hematology, b Department of Biomedicine, Experimental Hematology and c Institute of Pathology, University Hospital Basel, Basel, Switzerland In March 2006 a 57-year-old male was admitted to hos- pital, complaining of a short period of asthenia and night sweats. Laboratory analysis demonstrated markedly ele- vated leukocytes (37 ! 10 9 /l) with 87% of blasts, hemo- globin of 10.4 g/dl and thrombocytopenia of 43 ! 10 9 /l. Subsequent bone marrow investigation revealed domi- nant 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 un- remarkable, giving no evidence of recurrent genetic ab- normalities. The patient was treated on HOVON 42 Pro- tocol Arm A receiving 2 cycles of induction chemotherapy with cytarabine/idarubicin and cytarabine/amsacrine, respectively, which resulted in early first complete remis- sion. According to the protocol and due to the lack of an appropriate donor for allogeneic hematopoietic stem cell transplantation, therapy was completed with consolida- tion 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 mar- Myeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by increased proliferation of one to three hematopoietic cell lineages. The protein ty- rosine kinase JAK2 is mutated in virtually all patients with polycythemia vera and approximately 60% of pa- tients with primary myelofibrosis or essential thrombo- cythemia [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 my- eloid leukemia (AML) is a well-reported phenomenon. However, how JAK2 and other MPN-associated muta- tions contribute to disease progression is still the subject of debate [2–4]. In contrast, JAK2-positive MPN as sec- ondary 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 pathophysiol- ogy. Here we report the unique case of a 62-year-old pa- tient with secondary MPN harboring JAK2 V617F, which presented with isolated thrombocytosis 4 years after suc- cessful 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, pan- creatic cancer, associated with dysregulation in JAK/ STAT3 signaling. Received: June 18, 2012 Accepted: July 1, 2012 Published online: September 19, 2012 Dr. Sabine Girsberger University Hospital Basel, Hematology Petersgraben 4 CH–4031 Basel (Switzerland) E-Mail girsbergers  @  uhbs.ch © 2012 S. Karger AG, Basel 0001–5792/13/1291–0023$38.00/0 Accessible online at: www.karger.com/aha Downloaded by: Universitätsbibliothek Medizin Basel 131.152.211.61 - 10/10/2017 1:40:13 PM