**5. Summary**

FLT3/ITD+ AML can become refractory to *FLT3* inhibitors. Factors derived from the marrow microenvironment represent one such mechanism responsible for the refractory phenotype to *FLT3/ ITD* inhibitors. Understanding the molecular mechanism involved in microenvironment-mediated resistance will shed light on the development of innovative therapeutic strategies against FLT3/ITD+ AML, especially for FLT3/ITD+ AML that has become refractory to *FLT3* inhibitors.
