SPP1 and acute myeloid leukemia: Functionally, osteopontin was shown to upregulate AKT, mTOR, PTEN, and β-catenin mRNA expression in AML cells in vitro (113) and increase AML LSC self-renewal, proliferation, and expression of anti-apoptotic and cell-cycle-associated genes, thereby leading to accelerated disease progression in an MLL-AF9 driven AML mouse model (84).