A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis

Cai, Jiaoyang; Huang, Xia; Yin, Minzhi; Pan, Ci; Song, Lili; Zhan, Zhiyan; Chen, Jing; Gao, Yijin; Tang, Jingyan; Li, Yanxin; Shen, Shuhong

doi:10.1002/ijc.31636

Cited by 11 publications

(4 citation statements)

References 40 publications

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“…By comparing the clinical features of patients with MAP2K1 mutation and the BRAF V600E mutation, it was found that BRAF V600E -mutated LCH occurred earlier with a younger age of disease onset, and most of the patients had RO (especially liver) and skin involvement, while the patients with MAP2K1 mutation mostly had SS-multiple bone involvement. These results are similar to those of previous studies (Cai et al 2019).…”

Section: Discussionsupporting

confidence: 93%

Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children

Yang

Wang

et al. 2021

J Cancer Res Clin Oncol

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To analyze the genetic and clinical features of children with MAP2K1-mutated Langerhans cell histiocytosis (LCH). MethodsWe compared the clinical features of 37 children with MAP2K1-mutated LCH with those of the BRAF V600E mutation group (n = 133) and no known mutation group (n = 59) in the same period. ResultsWe found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53-62 and p.98-103.The most common mutation site was c.172_186del (12/37). Compared with the BRAF V600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single system multiple bone involvement (P = 0.022), with later disease onset (P = 0.029) as well as less involvement of risk organs, especially liver (P = 0.024). There was no signi cant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of rst-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1-mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769-22.526), P = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P = 0.688) and limb bone involvement (5/12 vs. 5/25, P = 0.240), were not correlated to disease progression or relapse. ConclusionThe children with MAP2K1-mutated LCH have speci c clinical features requiring clinical strati cation and precise treatment. MAP2K1-mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.

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Section: Discussionsupporting

confidence: 93%

Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children

Yang

Wang

et al. 2021

J Cancer Res Clin Oncol

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“…Other variants of BRAF have been described in LCH, including in‐frame deletions, fusions and duplications, 141 together with somatic mutations of MAP2K1 which, similar to BRAF, increase phosphorylation of ERK 155 . Other genetic alterations have been associated with LCH, such as the fusion gene PLEKHA6‐NTRK3, which is also able to activate the ERK pathway 156 …”

Section: Langerhans Cell Histiocytosismentioning

confidence: 99%

A clinical approach to parasellar lesions in the transition age

Sbardella

Puliani

Feola

et al. 2021

J Neuroendocrinology

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Many reviews have summarised the pathology and management of the parasellar region in adult patients, although an analysis of these aspects in the transition years, from puberty onset to the age of peak bone mass, has been lacking. A comprehensive search of English‐language original articles, published from 2000 to 2020, was conducted in the MEDLINE database (December 2019 to March 2020). We selected all studies regarding epidemiology, diagnosis and management of the following parasellar lesions: germinoma, craniopharyngioma, Langerhans cell histiocytosis, optic glioma, hypothalamic hamartoma, tuber cinereum hamartoma, cranial chordoma, Rathke cleft cyst, hypophysitis and hypothalamitis during the transition age from childhood to adulthood. In the present review, we provide an overview of the principal parasellar lesions occurring in the transition age. Symptoms are usually a result of the mass effect of the lesions on nearby structures, as well as anterior pituitary deficits. Diabetes insipidus occurs frequently in these patients. In this age group, pubertal developmental disorders may be more evident compared to other stages of life. Parasellar lesions in the transition age mostly include neoplastic lesions such as germinomas, hamartomas, optic gliomas, craniopharyngiomas Langerhans cell histiocytosis and chordomas, and rarely inflammatory lesions (hypophysitis, hypothalamitis). There are limited data on the management of parasellar lesions in the transition age. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life of the individual patient in this complex age range. The clinical approach to parasellar lesions involves a multidisciplinary effort.

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“… 7 Similar to ECD, kinase fusions ( BRAF, ALK, NTRK1 ), BRAF - duplications, insertions, deletions, and rare mutations in the PI3K-AKT-mTOR pathway have been reported in LCH as well. 7 , 11 , 12 These molecular discoveries have implications for the diagnosis and management of LCH, and in conjunction with other recent studies on LCH in adults, have necessitated an update of the existing recommendations.…”

Section: Introductionmentioning

confidence: 99%

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

Goyal

Tazi

Go³

et al. 2022

Blood

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Langerhans cell histiocytosis (LCH) can affect children and adults with wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography based imaging for staging and response assessment in majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with emerging role of targeted (BRAF- and MEK-inhibitor) therapies. Despite documented response to treatments, many patients struggle with high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

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A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis

Cited by 11 publications

References 40 publications

Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children

Clinical study of MAP2K1-mutated Langerhans cell histiocytosis in children

A clinical approach to parasellar lesions in the transition age

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

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