| Literature DB >> 21665148 |
Thomas Schmidt1, Behzad Kharabi Masouleh, Sonja Loges, Sandra Cauwenberghs, Peter Fraisl, Christa Maes, Bart Jonckx, Kim De Keersmaecker, Maria Kleppe, Marc Tjwa, Thomas Schenk, Stefan Vinckier, Rita Fragoso, Maria De Mol, Karolien Beel, Sérgio Dias, Catherine Verfaillie, Richard E Clark, Tim H Brümmendorf, Peter Vandenberghe, Shahin Rafii, Tessa Holyoake, Andreas Hochhaus, Jan Cools, Michael Karin, Geert Carmeliet, Mieke Dewerchin, Peter Carmeliet.
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.Entities:
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Year: 2011 PMID： 21665148 DOI： 10.1016/j.ccr.2011.05.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743