Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome

Walker, Sarah R.; Wang, Chen; Walradt, Trent; Hong, Bok Sil; Tanner, Justin R.; Levinsohn, Jonathan L.; Goh, Gerald; Subtil, Antonio; Lessin, Stuart R.; Heymann, Warren R.; Vonderheid, Eric C.; King, Brett; Lifton, Richard P.; Choi, Jaehyuk

doi:10.1182/blood-2015-06-654277

Cited by 56 publications

(47 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These patients (patients 1 and 2) had previously undergone RNA-Seq analysis of CD3-CD4+ cells, revealing activation of STAT3, STAT3 target genes, and Th2 cytokines in the phenotypically abnormal T cells (Walker, et al, 2015). The other 3 patients had idiopathic HES.…”

Section: Resultsmentioning

confidence: 99%

“…(Walker, et al, 2015) Specifically, we showed a gain-of-function mutation in STAT3 and overexpression of STAT3 gene targets that were necessary and sufficient for the production of eosinophil-promoting Th2 cytokines. Based on these data, we hypothesized that inhibitors of this pathway, namely the JAK inhibitors tofacitinib (JAK1/3 inhibitor) and ruxolitinib (JAK1/2 inhibitor), would be effective treatment of secondary HES.…”

Section: Introductionmentioning

confidence: 93%

“…(Roufosse, Cogan and Goldman, 2007) Lymphocytic variant HES (L-HES) is a subtype of secondary HES wherein the source of Th2 cytokines is a phenotypically abnormal CD4+ T cell (typically CD3-CD4+). (Simon, Plotz, Dummer and Blaser, 1999, Walker et al, 2015)…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib

King

Lee

Choi

2017

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib

King

Lee

Choi

2017

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

“…In most cases of L-HES, the T-lymphocytes are clonal. Recently, a gain-of-function STAT3 mutation was found in a patient with L-HES, and by cell sorting, the mutation was identified in the CD3-CD4+ T-cells [25]. Patients with L-HES usually present with skin lesions and rheu- matologic symptoms and less commonly with lymphadenopathy, gastrointestinal, and pulmonary symptoms.…”

Section: Secondary Hementioning

confidence: 99%

The Diagnostic Work-Up of Hypereosinophilia

Wang¹

2018

Pathobiology

View full text Add to dashboard Cite

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.

show abstract

“…It is unclear whether these two processes indicate a coincidental finding or have a pathogenic relationship. It is possible that IL-3 secretion by the Th2 cells in LV-HES patients can promote mast cell activation via STAT3 [6]; the STAT3 mutation (Y640F) may co-exist in aberrant T cells and mast cells in LV-HES patients [7]. …”

mentioning

confidence: 99%

A case of lymphocytic variant hypereosinophilic syndrome with sub-diagnostic systemic mastocytosis

Jain

Wang

Yin³

et al. 2017

Blood Res

View full text Add to dashboard Cite

Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome

Cited by 56 publications

References 17 publications

Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib

Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib

The Diagnostic Work-Up of Hypereosinophilia

A case of lymphocytic variant hypereosinophilic syndrome with sub-diagnostic systemic mastocytosis

Contact Info

Product

Resources

About