The Hypereosinophilic Syndromes

Hardy, W. Rod

doi:10.7326/0003-4819-68-6-1220

Cited by 460 publications

(179 citation statements)

References 17 publications

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“…[8][9][10][11][12] In spite of these, several responses to different agents, for example IFN-a, have been reported in patients without the involvement of PDGFR. 15 In this study we provide evidence that WT1 quantitative assessment is a powerful molecular marker able to distinguish between HES/CEL and the reactive forms of eosinophilia.…”

Section: Discussionmentioning

confidence: 91%

“…[9][10][11][12][13] In spite of this, in most patients with eosinophilia, no molecular lesions can be detected and the majority of them exhibit a normal karyotype by conventional cytogenetic, with only sporadic cases with clonal chromosomal abnormalities. 14 So far, for the majority of them, the diagnosis of HES is based on exclusion criteria 15 and in same cases it may remain doubt.…”

Section: Introductionmentioning

confidence: 99%

“…16 By contrast, it is overexpressed in many types of hematopoietic disorders including acute and chronic leukemias and myeloproliferative disorders. [7][8][9][10][11][12][13][14][15][16][17][18][19] At present, the quantitative assessment of WT1 transcript has been widely accepted as a useful tool for monitoring the presence of the reappearance of the leukemic clone in many hematological malignancies. [20][21][22][23][24] WT1 is, therefore, a molecular marker useful not only to monitor minimal residual disease in acute and chronic leukemias, but also represents a powerful tool for the detection of clonal myeloid disorders, which sometimes require a differential diagnosis from secondary or reactive conditions.…”

Section: Introductionmentioning

confidence: 99%

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WT1 transcript amount discriminates secondary or reactive eosinophilia from idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia

et al. 2007

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Idiopathic hypereosinophilic syndromes (HES) comprise a spectrum of indolent to aggressive diseases characterized by persistent hypereosinophilia. Hypereosinophilia can result from the presence of a defect in the hematopoietic stem cell giving rise to eosinophilia, it can be present in many myeloproliferative disorders or alternatively it may be a reactive form, secondary to many clinical conditions. The hybrid gene FIP1L1-PDGRFa was identified in a subset of patients presenting with HES or chronic eosinophilic leukemia (CEL). In spite of this, the majority of HES patients do not present detectable molecular lesions and for many of them the diagnosis is based on exclusion criteria and sometimes it remains doubt. In this study we explored the possibility to distinguish between HES/ CEL and reactive hypereosinophilia based on WT1 transcript amount. For this purpose, 312 patients with hypereosinophilia were characterized at the molecular and cytogenetic level and analyzed for WT1 expression at diagnosis and during follow-up. This study clearly demonstrates that WT1 quantitative assessment allows to discriminate between HES/CEL and reactive eosinophilia and represents a useful tool for disease monitoring especially in the patients lacking a marker of clonality.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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WT1 transcript amount discriminates secondary or reactive eosinophilia from idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia

et al. 2007

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“…3 The use of the term HES has evolved over the last 40 years since its first use by Hardy and Anderson to describe 3 patients with marked eosinophilia and eosinophilic cardiopulmonary involvement. 4 Not only have improved diagnostic techniques led to the identification of previously unrecognized causes of HES, but the availability of effective therapies has led to a marked decrease in morbidity and mortality in patients with HES who are treated early (before the development of irreversible complications). In an attempt to address these issues, updated definitions and classification systems for HES have been proposed by the World Health Organization (WHO), 5 consensus panels, 3 and other experts 6 (supplemental Table 1 available on the Blood Web site).…”

Section: Definitionsmentioning

confidence: 99%

How I treat hypereosinophilic syndromes

Klion

2015

Blood

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Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 × 109/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. HESs are pleomorphic in clinical presentation and can be idiopathic or associated with a variety of underlying conditions, including allergic, rheumatologic, infectious, and neoplastic disorders. Moreover, the etiology of the eosinophilia in HESs can be primary (myeloid), secondary (lymphocyte-driven), or unknown. Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. This review presents an updated treatment-based approach to the classification of patients with presumed HES and discusses the roles of conventional and novel agents in the management of these patients.

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“…heart, lung, skin) caused by eosinophilic tissue infiltration with release of cytoplasmic mediators. 1,2 Historically, therapy for patients with HES has encompassed the use of corticosteroids or interferon-alpha. 3 A subset of patients with HES harbor the abnormal FIP1-like-1 (FIP1L1)-platelet-derived growth factor receptor-alpha (PDGFR-a) fusion gene, resulting from an 800 kb cryptic interstitial deletion involving chromosome 4q12.…”

Section: Introductionmentioning

confidence: 99%

The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-α-expressing cells through caspase-3-mediated cleavage of Mcl-1

et al. 2007

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The FIP1-like-1 (FIP1L1)-platelet-derived growth factor receptoralpha (FIP1L1-PDGFR-a) fusion kinase causes hypereosinophilic syndrome (HES) in a defined subset of patients. Imatinib mesylate is a potent inhibitor of ABL but also of PDGFR-a, and has been associated with durable hematologic responses in patients with HES. However, development of mutations in the tyrosine kinase domain may hamper the activity of tyrosine kinase inhibitors (TKIs), which suggests that novel agents are warranted to prevent or overcome resistance. We evaluated the efficacy of the novel TKI EXEL-0862 in FIP1L1-PDGFR-aexpressing cell lines and in cells from a patient with HES harboring the FIP1L1-PDGFR-a gene. EXEL-0862 inhibited the proliferation of EOL-1 and imatinib-resistant T674I FIP1L1-PDGFR-a-expressing cells and resulted in potent inhibition of the phosphorylation of PDGFR-a and downstream proteins STAT3 and Erk1/2, both in vitro and ex vivo. Moreover, EXEL-0862 induced apoptotic death in EOL-1 cells and imatinibresistant T674I FIP1L1-PDGFR-a-expressing cells, and resulted in significant downregulation of the antiapoptotic protein Mcl-1 through a caspase-dependent mechanism. Our data establish EXEL-0862 as a solid candidate for the targeted treatment of patients with FIP1L1-PDGFR-a-positive HES.

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The Hypereosinophilic Syndromes

Cited by 460 publications

References 17 publications

WT1 transcript amount discriminates secondary or reactive eosinophilia from idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia

WT1 transcript amount discriminates secondary or reactive eosinophilia from idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia

How I treat hypereosinophilic syndromes

The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-α-expressing cells through caspase-3-mediated cleavage of Mcl-1

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