Thus, intra-tumoral heterogeneity, which is believed to underlie therapy resistance in many malignant tumors, also occurs in mTORC1-hyperactive AML and LAM, and combinatorial targeting mTORC1 and factors such as MDK that contribute to this heterogeneity may enhance the efficacy of mTORC1 inhibition. This evidence concerns the gene MDK and acute myeloid leukemia.