Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia.
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Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia. / Schmidt, Thomas; Behzad, Kharabi Masouleh; Loges, Sonja; Cauwenberghs, Sandra; Fraisl, Peter; Maes, Christa; Jonckx, Bart; Kim, De Keersmaecker; Kleppe, Maria; Tjwa, Marc; Schenk, Thomas; Vinckier, Stefan; Fragoso, Rita; Maria, De Mol; 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.
In: CANCER CELL, Vol. 19, No. 6, 6, 2011, p. 740-753.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia.
AU - Schmidt, Thomas
AU - Behzad, Kharabi Masouleh
AU - Loges, Sonja
AU - Cauwenberghs, Sandra
AU - Fraisl, Peter
AU - Maes, Christa
AU - Jonckx, Bart
AU - Kim, De Keersmaecker
AU - Kleppe, Maria
AU - Tjwa, Marc
AU - Schenk, Thomas
AU - Vinckier, Stefan
AU - Fragoso, Rita
AU - Maria, De Mol
AU - Beel, Karolien
AU - Dias, Sérgio
AU - Verfaillie, Catherine
AU - Clark, Richard E
AU - Brümmendorf, Tim H
AU - Vandenberghe, Peter
AU - Rafii, Shahin
AU - Holyoake, Tessa
AU - Hochhaus, Andreas
AU - Cools, Jan
AU - Karin, Michael
AU - Carmeliet, Geert
AU - Dewerchin, Mieke
AU - Carmeliet, Peter
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Cell Line, Tumor
KW - Bone Marrow Cells/metabolism
KW - Drug Resistance, Neoplasm
KW - Fusion Proteins, bcr-abl/physiology
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/etiology/metabolism/mortality
KW - NF-kappa B/physiology
KW - Osteolysis/prevention & control
KW - Piperazines/therapeutic use
KW - Pregnancy Proteins/antagonists & inhibitors/blood/physiology
KW - Pyrimidines/therapeutic use
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Cell Line, Tumor
KW - Bone Marrow Cells/metabolism
KW - Drug Resistance, Neoplasm
KW - Fusion Proteins, bcr-abl/physiology
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/etiology/metabolism/mortality
KW - NF-kappa B/physiology
KW - Osteolysis/prevention & control
KW - Piperazines/therapeutic use
KW - Pregnancy Proteins/antagonists & inhibitors/blood/physiology
KW - Pyrimidines/therapeutic use
M3 - SCORING: Journal article
VL - 19
SP - 740
EP - 753
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
M1 - 6
ER -