2026 - MS - Tracking BRAF V600E Persistence in Histiocytoses - Julien Haroche

In this scientific presentation from the Erdheim-Chester Disease Global Alliance (ECDGA), Dr. Julien Haroche presents research on tracking BRAF V600E persistence under MEK inhibition in histiocytosis, based on work from Florian Hodu and collaborators. This talk explores how mutated cells may persist during targeted therapy and how treatment may reshape where those cells are found within the blood and bone marrow compartments. Dr. Haroche explains that histiocytic disorders such as Erdheim-Chester Disease (ECD) and Langerhans Cell Histiocytosis (LCH) are driven by inflammatory cell accumulation and MAPK pathway mutations, including BRAF V600E. While BRAF and MEK inhibitors can produce deep responses, relapse after treatment interruption suggests that mutant clones may remain in the body even during therapy. This presentation covers important topics including: • Why BRAF V600E is important in ECD, LCH, and mixed histiocytosis • How targeted therapies have changed the treatment landscape for histiocytic disorders • Why relapse after treatment discontinuation raises questions about persistent mutant clones • How researchers track BRAF V600E using bone marrow and peripheral blood samples • The use of digital droplet PCR and single-cell DNA analysis to detect mutations • Evidence that BRAF V600E may persist across multiple hematopoietic lineages during MEK inhibition • How treatment may shift mutated cells toward the B-cell compartment • Longitudinal tracking of mutation distribution in peripheral blood cells • Transcriptomic findings suggesting a B-cell-like program in progenitor cells under treatment • How these findings may inform future research and therapeutic strategies Dr. Haroche also discusses how BRAF V600E-mutated cells may remain detectable in hematopoietic progenitors and peripheral blood cells despite MEK inhibitor treatment. The findings suggest that targeted therapy may not fully eliminate the mutation but may instead change the distribution of mutated cells across blood cell lineages, including possible enrichment in B-cell compartments. This video is part of ECDGA’s mission to raise awareness, provide education and support, and encourage research related to Erdheim-Chester Disease and related histiocytic disorders. The Erdheim-Chester Disease Global Alliance is a 501(c)(3) nonprofit organization dedicated to awareness, support, education, and research for those affected by ECD. Learn more about ECDGA, educational resources, events, research updates, and support opportunities at: https://www.erdheim-chester.org/ Disclaimer: The Erdheim-Chester Disease Global Alliance (ECDGA) does not provide medical advice, diagnoses, or treatments. All content is for informational purposes only. Please consult with a healthcare provider for medical concerns.