Title: Loss or Inhibition of Stromal-Derived PlGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1(+) Leukemia
Authors: Schmidt, Thomas *
Kharabi-Masouleh, Behzad *
Loges, Sonja *
Cauwenberghs, Sandra
Fraisl, Peter
Maes, Christa
Jonckx, Bart
De Keersmaecker, Kim
Kleppe, Ria
Tjwa, Marc
Schenk, Thomas
Vinckier, Stefan
Fragoso, Rita
De Mol, Maria
Beel, Karolien
Dias, Sérgio
Verfaillie, Catherine
Clark, Richard E
Brümmendorf, Tim H
Vandenberghe, Peter
Rafii, Shahin
Holyoake, Tessa
Hochhaus, Andreas
Cools, Jan
Karin, Michael
Carmeliet, Geert
Dewerchin, Mieke
Carmeliet, Peter # ×
Issue Date: Jun-2011
Publisher: Cell Press
Series Title: Cancer Cell vol:19 issue:6 pages:740-753
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.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Vesalius Research Centre (-)
Clinical and Experimental Endocrinology
Laboratory of Molecular Biology of Leukemia
Molecular and Vascular Biology
Hematology Section (-)
Interdepartemental Stem Cell Institute (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
* (joint) first author
× corresponding author
# (joint) last author

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