KIT D 816 V and JAK 2 V 617 F mutations are seen recurrently in hypereosinophilia of unknown significance

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 FIP1L1‐PDGFRA ( FP ) fusion gene also for KIT D816V and JAK2 V617F mutations. Overall, 86 (20%) patients tested positive: FP + in 55 (12%), KIT D816V+ in 14 (3%), and JAK2 V617F+ in 17 (4%) patients, respectively. To gain better insight into clinical characteristics, we compared these cases with 31 additional and well‐characterized KIT 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 FP + cases while abdominal lymphadenopathy, ascites, and serum tryptase levels >100 μg/l were characteristic for those with KIT D816V. Leukocytes, hemoglobin, and splenomegaly did not differ significantly. A median of three additional mutations, most frequently TET2 and SRSF2 , were identified in 12/13 KIT D816V+ SM‐eo patients with available material indicating a more complex molecular pathogenesis. Median survival was not reached for FP + cases but was only 26 and 41 months for KIT D816V+ SM and JAK2 V617F+ MPN‐eo, respectively. Eosinophilia of ≥2 × 10 9 /l was identified as discriminator for inferior survival in KIT D816V+ and/or JAK2 V617F+ patients (median survival 20 months vs. not reached, P  = 0.002). Thus, there is a clear prognostic and therapeutic rationale for detection of KIT D816V and JAK2 V617F in the diagnostic work up of eosinophilia. Am. J. Hematol. 90:774–777, 2015. © 2015 Wiley Periodicals, Inc.