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Date: Jul 01, 2010
New Model of Leukemia Sheds Light on Possible Novel Treatment Targets
MANHASSET, NY - Scientists at the Feinstein Institute for Medical Research have created a clever model of how leukemia cells hide in the bone marrow niche and then grow and divide throughout the human body. Sarah R. Vaiselbuh, MD, and her colleagues figured out a way to create a human to human microenvironment in the laboratory so that they can study the disease process and eventually use the model to test new treatments. The finding is published in the July issue of Tissue Engineering.
Dr. Sarah Vaiselbuh, Assistant Professor of Pediatrics, is flanked by Dr. Kevin Tracey, Director and Chief Executive Officer of the Feinstein Institute for Medical Research, and Associate Dean for Research and Professor of Molecular Medicine and Neurosurgery at the School of Medicine and Ralph Nappi, President of the North Shore-LIJ Health System Foundation.
Understanding how leukemia cells interact with the bone marrow microenvironment is key to understanding this common cancer. According to Dr. Vaiselbuh, leukemia cells hide in niches in the bone marrow where they take cover from chemotherapy. Once the storm is over, the dormant leukemia cells sneak out of their niches and begin growing and pushing beyond the territory of the bone marrow. The Feinstein scientists say that this might be one explanation for relapse in leukemia.
To test this theory, Dr. Vaiselbuh created in an ectopic human leukemic stem cell niche by seeding a three-dimensional polyurethane scaffold (kindly provided by Biomerix) with mesenchymal stem cells from normal human bone marrow. Once the scaffold is coated with the mesenchymal stem cells, the structure is introduced subcutaneously into the back pocket of a laboratory model. The mesenchymal stem cells in the scaffold create an ectopic human bone marrow microenvironment complete with fat cells and blood vessels. To analyze whether the ectopic human microenvironment can support the growth of human acute myeloid leukemia cells in the laboratory model, they inject human myeloid leukemia cells onto the scaffold and watch what the cells do. They discovered that the leukemia cells need the support of the niche microenvironment to grow. Surprisingly up till three months after injection, the human myeloid leukemia cells grew locally in the niche, showing preference to the human microenvironment above the host environment. But by four months they were invading bone marrow, spleen and liver of the host model.
"This model mimics the human pathophysiology of leukemia cells in the bone marrow," said Dr. Vaiselbuh. She went on to study the genetic signature of the leukemia cells to help explain how the cells become invasive. The hope, she says, is to identify new oncogenic targets that can translate into novel therapeutic approaches to improve patient outcome."
She said that this model of the human leukemia stem cell niche could be used to develop novel ways to treat leukemia and prevent its relapse.