New Findings in Mice Discover Bone Marrow may Help Chemotherapy, Stem Cell Transplants

New findings in mice suggest that it may be possible, according to recent research conducted by Washington University School of Medicine in St. Louis, to therapeutically target support cells in a particular niche. This could mean that a drug that nourishes support cells could encourage blood stem cells to establish themselves in the bone marrow, thus enabling patients who have had stem cell.

While tumor cells are known to hide in the bone marrow, and a drug that disrupts the niche environment may drive cancer cells into the bloodstream, they can often be more vulnerable to the damaging effects of chemotherapy. 

"Our results offer hope for targeting these niches to treat specific cancers or to improve the success of stem cell transplants," says senior author Daniel Link, MD, the Alan A. and Edith L. Wolff Professor of Medicine. "Already, we and others are leading clinical trials to evaluate whether it is possible to disrupt these niches in patients with leukemia or multiple myeloma." 

Working with mice, researchers deleted a critical gene, CXCL12, in certain support cells in the nice.

"What we found was rather surprising," Link says. "There's not just one niche for developing blood cells in the bone marrow. There's a distinct niche for stem cells, which have the ability to become any blood cell in the body, and a separate niche for infection-fighting blood cells that are destined to become T cells and B cells."

The findings provide a strong foundation for investigating whether disrupting these niches can improve the effectiveness of chemotherapy.

In a phase II pilot study led by Washington University medical oncologist Geoffrey Uy, MD, assistant professor of medicine, Link is evaluating whether the drug G-CSF can alter the stem cell niche in patients with acute lymphoblastic leukemia whose cancer has recurred or is resistant to treatment. The drug was approved by the Food and Drug Administration more than 20 years ago to stimulate production of white blood cells in patients undergoing chemotherapy, who often have weakened immune systems and are prone to infections.

However, Uy and colleagues will evaluate the drug when it is given before chemotherapy. Patients enrolled in the trial at the Siteman Cancer Centerwill receive G-CSF for five days before chemotherapy, and the investigators will determine whether it can disrupt the protective environment of the bone marrow niche and make cancer cells more sensitive to chemotherapy.