The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a small subset of myeloid/lymphoid neoplasms with eosinophilia

Schmitt‐Graeff, Annette; Erben, Philipp; Schwaab, Juliane; Vollmer-Kary, Beate; Metzgeroth, Georgia; Sotlar, Karl; Horny, Hans‐Peter; Kreipe, H.; Fisch, Paul; Reiter, Andreas

doi:10.1182/blood-2013-10-530642

Cited by 18 publications

(8 citation statements)

References 7 publications

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“…Indeed, mast cells and eosinophils may be found in both disorders; however, when present, genetic mutations (KIT mutations and FIP1L1-PDGFRa rearrangement) are the diseases distinctive signature (58). Only a few patients carry both KITD816V and FIP1L1-PDGFRa rearrangement (59). The delineation between FIP1L1-PDGFRa HES and KIT D816V advanced SM with eosinophilia has important clinical implications, as those with FIP1L1-PDGFRa rearrangement respond to imatinib and not the others (60).…”

Section: Treatment Of Advanced Smmentioning

confidence: 99%

Targeted Treatment Options in Mastocytosis

2017

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Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN). While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation) within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN). Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy.

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Section: Treatment Of Advanced Smmentioning

confidence: 99%

Targeted Treatment Options in Mastocytosis

2017

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“…Although disease-specific genetic mutations often guide diagnosis, limitations of cytogenetic criteria are emerging. One study showed that atypical MC microdissected from bone marrow of patients with F/P+ CEL harbored KIT D816V-mutated DNA in 5/19 cases [1].…”

Section: Diagnostic Criteria For Sm and Hesnmentioning

confidence: 99%

“…However, they are separate clinical entities, associated with different symptoms, signs, and prognosis and, most of the time, a specific underlying tyrosine kinase (TK) abnormality. Very rarely, these molecular abnormalities may coexist [1], and in some debatable cases, a single molecular lesion is detected, but morphological and immunologic criteria for both entities are fulfilled. The resulting confusion has led investigators to develop practical tools to help distinguish between primitive eosinophilic versus MC neoplasms [2].…”

Section: Introductionmentioning

confidence: 99%

Clonal eosinophil and mast cell diseases: different in the same way?

Wilde

Roufosse

Hermine

2016

Expert Review of Hematology

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“…These cases have been reported to have no KIT D816V mutations. However, microdissection of mast cells has revealed low levels of KIT D816V mutations in a subset of these cases [39]. Serum tryptase is often elevated.…”

Section: Myeloid/lymphoid Neoplasms Associated With Eosinophilia and mentioning

confidence: 99%

The Diagnostic Work-Up of Hypereosinophilia

Wang¹

2018

Pathobiology

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Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of ≥1.5 × 10⁹/L. HE can be one of the dominant manifestations of a hematopoietic myeloid neoplasm or secondary/reactive to an underlying medical condition. If a cause of HE and its associated tissue/organ damage is not determined, the condition is considered to be idiopathic hypereosinophilic syndrome (HES). The work-up of HE can be challenging due to a broad range of causes of HE that can be either reactive or neoplastic. In recent years, with the advent of molecular genetic testing and the introduction of targeted therapy in the management of these patients, there is a growing interest in better characterization of these diseases. Using a multimodality approach and following a proper algorithm, a diagnosis can be made in a large proportion of patients. In idiopathic HES, myeloid neoplasm associated somatic mutations as evidence of clonality are reported in 20–25% patients; however, the mutation data should be interpreted cautiously considering the prevalence of clonal hematopoiesis of indeterminate potential (CHIP). Bone marrow morphology has been shown to have important value in the identification of a true myeloid neoplasm in these disorders. A genome-wide study may be needed to understand the “idiopathic” cases that would ultimately lead to better patient care.

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The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a small subset of myeloid/lymphoid neoplasms with eosinophilia

Cited by 18 publications

References 7 publications

Targeted Treatment Options in Mastocytosis

Targeted Treatment Options in Mastocytosis

Clonal eosinophil and mast cell diseases: different in the same way?

The Diagnostic Work-Up of Hypereosinophilia

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