Actually, it can hide. CHLA’s Yong-Mi Kim tells us exactly how leukemia burrows within bone marrow, where it is shielded from cancer treatments. But given Kim’s breakthrough research on acute lymphoblastic leukemia, it won’t be able to hide forever.
Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, with more than 3,000 new cases reported each year. The majority of patients with ALL survive following chemotherapy treatments but some patients experience drug resistance and relapses in the disease. The most common cause of these unsuccessful outcomes? A researcher at Children’s Hospital Los Angeles says the answer lies in a patient’s own bones.
Yong-Mi Kim, MD, PhD, MPH, an investigator in the Children’s Center for Cancer and Blood Diseases at CHLA, explains. “Most relapse occurs in the bone marrow,” Kim says, “where the tissue harbors the leukemia cells and provides a safe haven that shelters them from chemotherapy.” She says that stromal cells within the marrow are known to be the culprits. “The question is, really, how they do it,” she says.
Kim, who is also an associate professor of pediatrics in the Keck School of Medicine of USC, leads a research team in studying integrins, molecules that line the surface of cells. These integrins bind to other cells, keeping them fixed in place. Her lab was the first to discover that one of these integrins, integrin alpha 4, anchors leukemia cells in the bone marrow, allowing them to become resistant to treatment. Because of this, Kim explains, ALL cells can lurk within the bone marrow for years, lying dormant until they reappear, causing a dangerous, often deadly, relapse in the disease. For this reason, Kim feels it is a mistake to look only at the cancer cells in leukemia research.
“Our lab is different from others because we try to see things from the perspective of the environment surrounding the leukemia cells,” Kim says. Now that she has established a role for integrin alpha 4, she has her sights set on finding other integrins that likely aid in the process of shielding ALL cells from chemotherapy. Once all the key players are identified, treatments can be devised to block the activity of these integrins, so leukemia will have nowhere to hide.
Chemotherapy comes with a long list of side-effects and possible long-term effects. Still, no one can doubt the high success rate in pediatric patients, estimated to be about 85-90%. But Kim does not find this to be acceptable. “Overall, children do very well but we are still failing around 10-15% of them,” she says, “and every child counts.”
Kim’s work can be found published in top cancer journals, such as Nature’s Leukemia, and she was recently awarded a $1.2M grant from the National Institute of Health’s National Cancer Institute. Projects covered by the grant will seek to pinpoint which integrins will make for the best treatment targets. “We want to harness this knowledge, target these molecules, and eventually make it to a clinical trial,” Kim explains.
Image: leukemia cells (green) hide within bone marrow (red); provided by Dr. Yong-Mi Kim of CHLA