Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia.

ABSTRACT: Despite the success of imatinib mesylate (IM) in the early chronic phase of chronic myeloid leukemia (CML), patients are resistant to IM and other kinase inhibitors in the later stages of CML. Our findings indicate that inhibition of Janus kinase 2 (Jak2) in Bcr-Abl+ cells overcomes IM resistance although the precise mechanism of Jak2 action is unknown. Knocking down Jak2 in Bcr-Abl+ cells reduced levels of the Bcr-Abl protein and also the phosphorylation of Tyr177 of Bcr-Abl, and Jak2 overexpression rescued these knockdown effects. Treatment of Bcr-Abl+ cells with Jak2 inhibitors for 4-6 h but not with IM also reduced Bcr-Abl protein and pTyr177 levels. In vitro kinase experiments performed with recombinant Jak2 showed that Jak2 readily phosphorylated Tyr177 of Bcr-Abl (a Jak2 consensus s

SUBMITTER: Samanta A 

PROVIDER: S-EPMC3072513 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature