In this issue of Blood, the findings of Chakraborty et al and Emile et al support a model in which the mitogen-activated protein kinase (MAPK) and PI3K/AKT pathways are critical in the pathogenesis of 2 of the most common histiocytoses—Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD)—whereas their respective mutational profiles demonstrate important similarities and differences.
Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signaling in ECD.