Hypothesis on the cell of origin in high- and low-risk LCH. Based on the results described in this paper, both low-risk (left part) and high-risk (right part) LCH are caused by somatically mutated oligopotent progenitor cells originating in the BM, such as the LMPP or (G)MODP. Progeny formed in the BM and/or at the tissue site that these progenitor cells are recruited to after mobilization into the blood determines the composition of myeloid cell types in the lesion. As shown here and supported by Halbritter et al,⁸  both high-risk and low-risk LCH lesions may contain the same diversity of mutation-carrying differentiated myeloid cell types, including OCs and MΦs. The different disease manifestations between high- and low-risk LCH may be due to significant differences in the frequencies of mutated progenitor cells and their place in the hematopoietic tree and may be reflected in the frequency and type of mutated end-differentiated cell types present.