Using specifically expressed cre, such as Prx1-cre (Greenbaum et al., 2013), nestin-cre (Méndez-Ferrer et al., 2010), Lepr-cre (Ding et al., 2012), and Osterix-cre (Tang et al., 2016), to induce PTPN11 mutations in bone marrow mesenchymal cells leads to MPN, but SHP2 mutations in endothelial cells (VE-Cadherin-cre) and osteoblasts (Oc-cre) will not lead to MPN formation (Dong et al., 2016), which indicates that SHP2 mutations in the specific components of bone marrow microenvironment show leukemogenic effects (Figure 3). This evidence concerns the gene NES and myeloproliferative disorder.