Cell of origin in histiocytic disorders. Expression of BRAF^V600E in terminally differentiated myeloid cells does not lead to cellular proliferation, whereas early expression of mutant BRAF (in MPP) gives rise to multiple hematologic tumors (Badalian-Very, unpublished data). Somatic mutation of BRAF^V600E in LCH and ECD is an early event that occurs in bone marrow progenitor cells. The cell of origin of both LCH and ECD is a matter of debate, but progenitor cells that give rise both to dendritic cells and macrophages is a strong candidate. Concomitant presence of LCH and ECD, better known as MH, also points to a biological link between these so-called distinct histiocytic disorders and suggest a common precursor cell for these diseases. Further studies are required to determine the additional factors that influence clinical presentation and disease outcome of mixed histiocytic disorders. CMP, common myeloid progenitor; MPP, multipotent progenitor.