Taken together, our data suggest that the inhibition of the pathways regulated by PKC kinase, CDK1 to 7, and CRM1/XPO1 are critical to overcome BM-mediated drug resistance of AML cells against daunorubicin in both the mesenchymal/fibroblastic and osteoblast niches. The gene discussed is XPO1; the disease is acute myeloid leukemia.