Skip to main content
. Author manuscript; available in PMC: 2016 Mar 5.
Published in final edited form as: Cell Stem Cell. 2015 Mar 5;16(3):254–267. doi: 10.1016/j.stem.2015.02.014

Figure 2. Models of disease initiation.

Figure 2

The majority of myeloid malignancies are caused by genetic lesions (stars) occurring in hematopoietic cells, which lead to BM niche remodeling and formation of LSCs with deranged perception of the microenvironment. Genetic lesions can also occur in stromal cells and lead to myeloid malignancies with predisposition to secondary mutations in hematopoietic cells. These two modes of disease initiation are not mutually exclusive as they share several common mechanisms and self-reinforcing loops including deregulated Notch/Wnt signaling and increased production of pro-inflammatory cytokines. Congenital lesions present in both hematopoietic and stromal cells are also observed in myeloid malignancies, and likely synergize as well as predispose for additional transforming lesions and more aggressive diseases. Arrows indicate the directionality of these events.