BM stromal cells enhance HIF-1α expression under hypoxia, leading to an HIF-1α-dependent upregulation of glucose transport and a switch to glycolytic metabolism in leukaemic cells and primary ALL blasts. Downregulation of HIF-1α expression or blockade of mTOR signalling with everolimus promoted chemosensitivity. Here, MTOR is linked to acute lymphoblastic leukemia.