In CML, however, osteoblasts are reported to confer niche-mediated LSC resistance against TKIs, and the dual PI3K and mTOR inhibitor BEZ235, which inhibits osteoblastic and endothelial cells in the BM microenvironment, enhances sensitivity of primary CML LSCs to TKI therapy [85]. This evidence concerns the gene MTOR and chronic myelogenous leukemia, BCR-ABL1 positive.