Author/Authors :
Schmidt، نويسنده , , Thomas and Masouleh، نويسنده , , Behzad Kharabi and Loges، نويسنده , , Sonja and Cauwenberghs، نويسنده , , Sandra and Fraisl، نويسنده , , Peter and Maes، نويسنده , , Christa and Jonckx، نويسنده , , Bart and De Keersmaecker، نويسنده , , Kim and Kleppe، نويسنده , , Maria and Tjwa، نويسنده , , Marc and Schenk، نويسنده , , Thomas and Vinckier، نويسنده , , Stefan and Fragoso، نويسنده , , Rita and De Mol، نويسنده , , Maria and Beel، نويسنده , , Karolien and Dias، نويسنده , , Sérgio and Verfaillie، نويسنده , , Catherine and Clark، نويسنده , , Richard E. and Brümmendorf، نويسنده , , Tim H. and Vandenberghe، نويسنده , , Peter and Rafii، نويسنده , , Shahin and Holyoake، نويسنده , , Tessa and Hochhaus، نويسنده , , Andreas and Cools، نويسنده , , Jan and Karin، نويسنده , , Michael and Carmeliet، نويسنده , , Geert and Dewerchin، نويسنده , , Mieke and Carmeliet، نويسنده , , Peter، نويسنده ,
Abstract :
Summary
ib 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.
