Advances in our understanding of genetic markers and targeted therapies for pediatric LCH.
Expert Rev Hematol
; 17(6): 223-231, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38721670
ABSTRACT
INTRODUCTION:
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. AREAS COVERED 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. EXPERT OPINION 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histiocytosis, Langerhans-Cell
/
Molecular Targeted Therapy
Limits:
Child
/
Humans
Language:
En
Journal:
Expert Rev Hematol
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country: