Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis
| العنوان: | Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis |
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| المؤلفون: | Zhaoxing Wu, Tao Chen, Weiwei Zheng, Ying Gu, Xiaoxian Gan, Xiaoya Lu, Zhipeng Meng, Xiaoxiao Ma, Wendong Huang, Jiawei Zhang, R Xu |
| المصدر: | Leukemia. 30:1282-1289 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_specialty, Biology, Fusion gene, Mice, 03 medical and health sciences, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Internal medicine, medicine, Animals, Humans, Cell Self Renewal, Phosphorylation, Hematology, Kinase, Myeloid leukemia, medicine.disease, Haematopoiesis, Leukemia, 030104 developmental biology, Oncology, Immunology, Neoplastic Stem Cells, Cancer research, Heterografts, Stem cell, Blast Crisis, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cyclin-Dependent Kinase Inhibitor p27 |
| الوصف: | 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 IIγ (CaMKIIγ). Genetic deletion of CaMKIIγ greatly inhibits disease progression via selectively impairing the self-renewal of leukemia stem cells (LSCs) in mouse models, whereas overexpression of CaMKIIγ has the opposite effects. In human CML, phosphorylated CaMKIIγ abundance is significantly associated with BC. Moreover, CaMKIIγ phosphorylates and reduces the nuclear cyclin-dependent kinase inhibitor p27Kip1, a critical brake that maintains LSC quiescence. These findings suggest that CaMKIIγ might be an important switch for the transition of CML BC and identify a unique mechanism by which CaMKIIγ promotes the self-renewal of LSCs by deceasing nuclear p27Kip1 to wake up dormant LSCs. Therefore, CaMKIIγ may provide a new therapeutic target to treat CML BC. |
| تدمد: | 1476-5551 0887-6924 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::160903a78879c8e0e0233330a673108d https://doi.org/10.1038/leu.2016.53 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....160903a78879c8e0e0233330a673108d |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765551 08876924 |
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