In the past, it was always thought that this was the result of PTPN11 activating mutations in HSCs, but we recently found that activating mutation of PTPN11 in MSCs, not HSCs, activates HSCs through long-term pro-inflammatory signals from MSCs and monocytes, which leads to excessive activation and proliferation of HSCs and the eventual progression to MPN (Dong et al., 2016). Here, PTPN11 is linked to myeloproliferative disorder.