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Cancer drug boosts levels of vascular-protective gene, KLF2
Date:6/11/2014

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She took her curious, yet pleasantly surprising, observation regarding bortezomib's thromboprotective effect to the laboratory. In her investigations, Nayak first showed that bortezomib treatment rendered normal mice resistant to clot formation. Next, she demonstrated that among the 17 members of the KLF family, bortezomib specifically and potently induced KLF2 levels. Finally, she confirmed the importance of KLF2 by injecting bortezomib into mice missing the KLF2 gene. Although bortezomib treatment protected normal mice from thrombosis, this effect was absent in the KLF2-deficient mice. "This taught us how important KLF2 is for the ability of bortezomib to protect against thrombosis," Nayak said.

The results of this study have the potential to alter the management of thrombosis in patients who have a predisposition to clot formation and especially in situations where present modalities of therapy are inadequate. One example of such a condition is antiphospholipid antibody syndrome (APLS), a condition where patients have an increased risk for blood clots in both arteries and veins. The disease often affects young women, and there is no effective antithrombotic strategy for this group of patients. Moreover, currently used antithrombotic therapies are associated with an increased risk for bleeding. Although bortezomib protects against thrombosis, it comes with no concurrent increase in bleeding, making this drug a potential treatment alternative for APLS patients.

"Vascular clots are the No. 1 cause of death and disability worldwide," Nayak said. "Our studies show that increasing KLF2 levels provides a favorable thromboprotective effect."

At present, KLF2 levels can be pharmacologically altered with bortezomib. Importantly, the study showed that bortezomib can induce KLF2 levels and provide protection against thrombosis, even when used at much lower doses than those used to treat patients with myeloma.

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Contact: Jeannette Spalding
jeannette.spalding@case.edu
216-368-3004
Case Western Reserve University
Source:Eurekalert

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