KITD816V andJAK2V617F mutations are seen recurrently in hypereosinophilia of unknown significance

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 and Reiter, Andreas (2015) KITD816V andJAK2V617F mutations are seen recurrently in hypereosinophilia of unknown significance. American Journal of Hematology, 90 (9), 774-777. (doi:10.1002/ajh.24075). (PMID:26017288)

Abstract

Purpose: 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.

Results: 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 >100µg/l were characteristic for those with KIT D816V. Leukocytes, hemoglobin and splenomegaly did not differ significantly. A median of 3 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 ?2x109/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).

Conclusion: thus, there is a clear prognostic and therapeutic rationale for detection of KIT D816V and JAK2 V617F in the diagnostic work up of eosinophilia

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Contributors

Author: Nicholas C.P. Cross

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