Concomitant chromosome 5q-deletion and JAK2V617F mutation present with myelodysplastic and myeloproliferative overlap features

Myelodysplastic Syndrome (MDS) with an isolated deletion of chromosome 5q [del(5q)] is a relatively rare MDS variant (5%) characterized by a moderate to severe anemia and normal or elevated platelet count with modest neutropenia [1-3]. These latter features, in addition to its excellent response to lenalidomide, are likely what contribute for its favorable prognosis [3-5]. The somatic gain of function mutation in JAK2 V617F is a driving mutation in Myeloproliferative Neoplasms (MPN), occurring in 97% of polycythemia vera (PV), 50-60% of essential thrombocytosis (ET) and primary myelofibrosis (PMF) [6]. This mutation results in constitutive activation of the JAK-STAT signaling pathway leading to increased proliferation and hypersensitivity to cytokines erythropoietin, IL-3, thrombopoietin, and GCSF. An allelic burden of JAK2 V617F mutation correlates with an increased risk of thrombosis and hemorrhage, as well as secondary fibrosis in MPN patients [7]. Compared to MPNs, JAK2 mutations are Laura Miotke1 ; Jay Patel2 ; Josef T Prchal3 ; Srinivas K Tantravahi1 * 1 Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. 2 Department of Pathology ARUP Laboratories, University of Utah, Salt Lake City, UT, USA. 3 Division of Hematology and Hematologic Malignancies, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT, USA. infrequent in MDS, occurring in less than 5% of the cases. This frequency is mirrored in the del(5q) subtype [8,9]. Concomitant presence of JAK2 V617F and del(5q) has been reported in the literature, although not much is known about how the prognosis of this combination differs from an isolated del(5q); and in particular with the risk of transformation to Acute Myeloid Leukemia (AML) and response to lenalidomide therapy. While classified as an MDS subset, patients with this combination exhibit specific clinical and pathologic features characteristic of both MDS and MPN. There have been reports that these patients present with a more proliferative bone marrow and retain morphologic features of MPN even after transformation to AML [10,11]. Here we describe two patients with a concomitant JAK2 V617F mutation and del5(q), both presenting with severe macrocytic anemia, marked thrombocytosis and characteristic bone marrow morphology.