Cell of origin in histiocytic disorders. Expression of BRAFV600E 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whereas early expression of mutant BRAF (in MPP) gives rise to multiple hematologic tumors (Badalian-Very, unpublished data).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 BRAFV600E 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.