Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1⁺leukemia

Schmidt, T. et al. (2011) Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1⁺leukemia. Cancer Cell, 19(6), pp. 740-753. (doi: 10.1016/j.ccr.2011.05.007)

Abstract

Imatinib has revolutionized the treatment of Bcr-Abl1⁺ chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PlGF levels are elevated in CML and that PlGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PlGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of Bcr-Abl1 signaling. Anti-PlGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PlGF inhibition for (imatinib-resistant) CML.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Holyoake, Professor Tessa
• Authors: Schmidt, T., Masouleh, B.K., Loges, S., Cauwenberghs, S., Fraisl, P., Maes, C., Jonckx, B., De Keersmaecker, K., Kleppe, M., Tjwa, M., Schenk, T., Vinckier, S., Fragoso, R., De Mol, M., Beel, K., Dias, S., Verfaillie, C., Clark, R.E., Brummendorf, T.H., Vandenberghe, P., Rafii, S., Holyoake, T.L., Hochhaus, A., Cools, J., Karin, M., Carmeliet, G., Dewerchin, M., and Carmeliet, P.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Cell
• Publisher: Cell Press
• ISSN: 1535-6108
• ISSN (Online): 1878-3686

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