Hartman Institute for Therapeutic Organ Regeneration

Activation of the vascular niche supports leukemic progression and resistance to chemotherapy.

TitleActivation of the vascular niche supports leukemic progression and resistance to chemotherapy.
Publication TypeJournal Article
Year of Publication2014
AuthorsPoulos MG, Gars EJ, Gutkin MC, Kloss CC, Ginsberg M, Scandura JM, Rafii S, Butler JM
JournalExp Hematol
Volume42
Issue11
Pagination976-986.e3
Date Published2014 Nov
ISSN1873-2399
KeywordsAngiogenesis Inhibitors, Animals, Antineoplastic Agents, Bone Marrow, Cell Adhesion, Cell Line, Transformed, Cell Proliferation, Cellular Microenvironment, Clone Cells, Coculture Techniques, Disease Models, Animal, Drug Resistance, Neoplasm, Gene Expression Regulation, Leukemic, Human Umbilical Vein Endothelial Cells, Humans, Leukemia, Myeloid, Acute, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplastic Stem Cells, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2
Abstract

<p>Understanding the intricate cellular components of the bone marrow microenvironment can lead to the discovery of novel extrinsic factors that are responsible for the initiation and progression of leukemic disease. We have shown that endothelial cells (ECs) provide a fertile niche that allows for the propagation of primitive and aggressive leukemic clones. Activation of the ECs by vascular endothelial growth factor (VEGF)-A provides cues that enable leukemic cells to proliferate at higher rates and also increases the adhesion of leukemia to ECs. Vascular endothelial growth factor A-activated ECs decrease the efficacy of chemotherapeutic agents to target leukemic cells. Inhibiting VEGF-dependent activation of ECs by blocking their signaling through VEGF receptor 2 increases the susceptibility of leukemic cells to chemotherapy. Therefore, the development of drugs that target the activation state of the vascular niche could prove to be an effective adjuvant therapy in combination with chemotherapeutic agents.</p>

DOI10.1016/j.exphem.2014.08.003
Alternate JournalExp Hematol
PubMed ID25179751
PubMed Central IDPMC4254082
Grant ListR01 HL097797 / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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