Janus Kinase 2: A Critical Target in Chronic Myelogenous Leukemia

作者: Ajoy K. Samanta , Hui Lin , Tong Sun , Hagop Kantarjian , Ralph B. Arlinghaus

DOI: 10.1158/0008-5472.CAN-06-0025

关键词: Chronic myelogenous leukemiaJanus kinase 2GSK-3GAB2Janus kinaseTyrosine kinaseProtein kinase BCancer researchImatinib mesylateMedicineOncology

摘要: The Bcr-Abl tyrosine kinase is the causative factor in most chronic myelogenous leukemia (CML) patients. We have shown that associated with a cluster of signaling proteins, including Janus (Jak) 2, growth receptor binding protein 2-associated binder (Gab) Akt, and glycogen synthase (GSK)-3beta. Treatment CML cell lines mouse Bcr-Abl+ 32D cells either Jak2 short interfering RNA or inhibitor AG490 inhibited pTyr Gab2 pSer Akt formation, activation nuclear factor-kappaB, caused GSK-3beta, leading to reduction c-Myc. Importantly, BaF3 expressing T315I E255K imatinib-resistant mutants underwent apoptosis on exposure yet were resistant imatinib. Similar wild-type cells, inhibition by Ag490 treatment resulted decrease c-Myc cells. These results identify as potentially important therapeutic target for CML.

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