Division of Haematology-Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Division of Haematology-Oncology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Expert Rev Hematol. 2024 Jun;17(6):223-231. doi: 10.1080/17474086.2024.2353772. Epub 2024 May 11.
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm, encompassing a diverse clinical spectrum ranging from localized bone or skin lesions to a multisystemic life-threatening condition. Over the past decade, there has been an expansion in understanding the molecular biology of LCH, which translated into innovative targeted therapeutic approaches.
In this article, we will review the molecular alterations observed in pediatric LCH and the relationship between these molecular changes and the clinical phenotype, as well as targeted therapies in LCH.
Mitogen-activated protein kinase (MAPK) pathway mutation is a hallmark of LCH and is identified in 80% of the cases. Notably, BRAFV600E mutation is seen in ~50-60% of the cases, ~30% has other MAPK pathway mutations, while 15-20% have no detected mutations. While the first line therapeutic approach is vinblastine and prednisone, targeted therapies - specifically BRAF/MEK inhibitors - emerged as a promising second-line salvage strategy, particularly when a mutation is identified. Most patients respond to BRAF/MEK inhibitors but at least 75% reactivate after stopping, however, most patients respond again when restarting inhibitors.
朗格汉斯细胞组织细胞增生症（LCH）是一种罕见的髓系肿瘤，其临床表现多样，从局限性骨或皮肤病变到危及生命的多系统疾病。在过去的十年中，人们对 LCH 的分子生物学有了更深入的了解，这转化为创新的靶向治疗方法。
本文将回顾儿科 LCH 中观察到的分子改变，以及这些分子变化与临床表型之间的关系，以及 LCH 的靶向治疗。
丝裂原活化蛋白激酶（MAPK）通路突变是 LCH 的标志，在 80%的病例中可检测到。值得注意的是，BRAFV600E 突变见于约 50-60%的病例，约 30%的病例存在其他 MAPK 通路突变，而 15-20%的病例未检测到突变。虽然一线治疗方法是长春碱和泼尼松，但靶向治疗——特别是 BRAF/MEK 抑制剂——作为一种有前途的二线挽救策略出现，特别是在检测到突变时。大多数患者对 BRAF/MEK 抑制剂有反应，但停药后至少有 75%会重新激活，然而，当重新开始抑制剂治疗时，大多数患者再次有反应。
