Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway.

ABSTRACT: Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cytokines, which may contribute to drug resistance. In current study, we utilized in vitro K562 co-culture model with BM stroma to investigate IM resistance. As a result, co-culturing of K562 with BM stroma was sufficient to cause resistance to IM, which was accompanied with the activation of hedgehog (Hh) signaling pathway and upregulation of BCR-ABL as well as its downstream proteins like phosphorylated Akt, Bcl-xL and survivin, etc. On the other hand, oroxyloside A (OAG)

SUBMITTER: Zhang X 

PROVIDER: S-EPMC5554535 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature