Glivec Research Today is a free monthly online journal that collates and summarizes the latest research about Glivec, including details on gleevec, imatinib, cancer, treatment, side-effects.

Janus kinase 2: a critical target in chronic myelogenous leukemia.

Samanta AK, Lin H, Sun T, Kantarjian H, Arlinghaus RB

Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

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

Published 4 July 2006 in Cancer Res, 66(13): 6468-72.
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