KITD816V and JAK2V617F mutations are seen recurrently in hypereosinophilia of unknown significance. Issue 9 (14th August 2015)

• Record Type: Journal Article
• Authors: Schwaab, Juliana; Umbach, Roland; Metzgeroth, Georgia; Naumann, Nicole; Jawhar, Mohamad; Sotlar, Karl; Horny, Hans‐Peter; Gaiser, Timo; Hofmann, Wolf‐Karsten; Schnittger, Susanne; Cross, Nicholas C.P.; Fabarius, Alice; Reiter, Andreas
• Is Part Of: American journal of hematology. Volume 90:Issue 9(2015:Sep.)
• Page Start: 774
• Page End: 777
• Publication Date: 2015-08-14
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24075
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Myeloproliferative neoplasms with eosinophilia are commonly characterized by a normal karyotype and remain poorly defined at the molecular level. We therefore investigated 426 samples from patients with hypereosinophilia of unknown significance initially referred for screening of the <italic>FIP1L1‐PDGFRA</italic> (<italic>FP</italic>) fusion gene also for <italic>KIT</italic> D816V and <italic>JAK2</italic> V617F mutations. Overall, 86 (20%) patients tested positive: <italic>FP</italic>+ in 55 (12%), <italic>KIT</italic> D816V+ in 14 (3%), and <italic>JAK2</italic> V617F+ in 17 (4%) patients, respectively. To gain better insight into clinical characteristics, we compared these cases with 31 additional and well‐characterized <italic>KIT</italic> D816V+ eosinophilia‐associated systemic mastocytosis (SM‐eo) patients enrolled within the "German Registry on Disorders of Eosinophils and Mast cells." Significant differences included younger age, male predominance, and higher eosinophil counts for <italic>FP</italic>+ cases while abdominal lymphadenopathy, ascites, and serum tryptase levels >100 μg/l were characteristic for those with <italic>KIT</italic> D816V. Leukocytes, hemoglobin, and splenomegaly did not differ significantly. A median of three additional mutations, most frequently <italic>TET2</italic> and <italic>SRSF2</italic>, were identified in 12/13 <italic>KIT</italic> D816V+ SM‐eo patients with available material indicating a more complex molecular pathogenesis. Median survival was not reached for <italic>FP</italic>+ cases but was only 26 and 41 months for <italic>KIT</italic> D816V+ SM and <italic>JAK2</italic> V617F+ MPN‐eo, respectively. Eosinophilia of ≥2 × 10<sup>9</sup>/l was identified as discriminator for inferior survival in <italic>KIT</italic> D816V+ and/or <italic>JAK2</italic> V617F+ patients (median survival 20 months vs. not reached, <italic>P</italic> = 0.002). Thus, there is a clear prognostic and therapeutic rationale for detection of <italic>KIT</italic> D816V and <italic>JAK2</italic> V617F in the diagnostic work up of eosinophilia. Am. J. Hematol. 90:774–777, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>