| First Author | Gu Y | Year | 2016 |
| Journal | Leukemia | Volume | 30 |
| Issue | 6 | Pages | 1282-9 |
| PubMed ID | 27012864 | Mgi Jnum | J:231907 |
| Mgi Id | MGI:5775489 | Doi | 10.1038/leu.2016.53 |
| Citation | Gu Y, et al. (2016) Aberrant activation of CaMKIIgamma accelerates chronic myeloid leukemia blast crisis. Leukemia 30(6):1282-9 |
| abstractText | Blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), but its molecular basis remains poorly understood. Here, we show that CML BC is regulated by calcium-calmodulin-dependent kinase IIgamma (CaMKIIgamma). Genetic deletion of CaMKIIgamma greatly inhibits disease progression via selectively impairing the self-renewal of leukemia stem cells (LSCs) in mouse models, whereas overexpression of CaMKIIgamma has the opposite effects. In human CML, phosphorylated CaMKIIgamma abundance is significantly associated with BC. Moreover, CaMKIIgamma phosphorylates and reduces the nuclear cyclin-dependent kinase inhibitor p27Kip1, a critical brake that maintains LSC quiescence. These findings suggest that CaMKIIgamma might be an important switch for the transition of CML BC and identify a unique mechanism by which CaMKIIgamma promotes the self-renewal of LSCs by deceasing nuclear p27Kip1 to wake up dormant LSCs. Therefore, CaMKIIgamma may provide a new therapeutic target to treat CML BC. |
