These observations indicate that targeting the CXCL12/CXCR4 axis is a promising strategy to overcome extrinsic resistance by the protective BM microenvironment in FLT3-ITD-AML through sensitizing leukemic cells to FLT3 inhibitors, contrasting diverse combination strategies focusing on intrinsic resistance mechanisms, such as the acquisition of point mutations in ATP binding regions of the FLT3 kinase domain, mutations in other kinases, the upregulation of parallel pro-survival pathways, upregulation of the FLT3 receptor, and activation of antiapoptotic proteins [23]. Here, CXCL12 is linked to acute myeloid leukemia.