Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia. Academic Article uri icon

Overview

MeSH

  • Animals
  • Benzamides
  • Bone Marrow Cells
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Humans
  • Imatinib Mesylate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B
  • Osteolysis
  • Placenta Growth Factor

MeSH Major

  • Fusion Proteins, bcr-abl
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Piperazines
  • Pregnancy Proteins
  • Pyrimidines

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. Copyright © 2011 Elsevier Inc. All rights reserved.

publication date

  • June 14, 2011

has subject area

  • Animals
  • Benzamides
  • Bone Marrow Cells
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B
  • Osteolysis
  • Piperazines
  • Placenta Growth Factor
  • Pregnancy Proteins
  • Pyrimidines

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2011.05.007

PubMed ID

  • 21665148

Additional Document Info

start page

  • 740

end page

  • 753

volume

  • 19

number

  • 6