Patients diagnosed with the most common form of leukemia who also have high levels of an enzyme known to suppress the immune system are most likely to die early, researchers say.
High levels of this enzyme, indoleamine 2,3 dioxygenase, or IDO, at diagnosis also identify those who might benefit most by taking an IDO inhibitor along with their standard therapy, they report in the Nature journal Scientific Reports.
"We want to help people who are not responding to treatment and are dying very soon after their diagnosis," says Dr Ravindra Kolhe, breast and molecular pathologist and director of the Georgia Esoteric & Molecular Labs LLC in the Department of Pathology at the Medical College of Georgia at Augusta University.
A review of 40 patients with acute myeloid leukemia, or AML, found increased IDO expression in the bone marrow biopsy, performed to diagnose their disease, correlated with lower overall survival rates and early mortality.
It also indicates that IDO expression should routinely be measured when the diagnostic bone marrow biopsy is performed, Kolhe says.
An early phase clinical study already is underway to begin to explore the IDO inhibitor's clinical potential in these patients. Sites include the Georgia Cancer Center at MCG as well as Johns Hopkins University and the University of Maryland Schools of Medicine, both in Baltimore. NewLinks Genetics Corp., a biopharmaceutical company based in Ames, Iowa that produces the inhibitor Indoximod, is funding the study.
"We wanted to look at what makes this leukemia so aggressive that initial induction chemotherapy is not working," Kolhe says. "Early relapse tends to predict early mortality in these patients and one of the things we looked at was IDO," says the study's corresponding author.
While everyone has the IDO gene, it's the cancer cells in this scenario that activate the disabler of the immune response that is also used by the fetus and solid tumors, he says.
Stem cells in the bone marrow are supposed to mature into a variety of cells that enable our blood and immune system function. Instead in AML, stem cells get stuck in an in-between, undifferentiated state called blasts.
"It's very normal to go to the blast step, providing it matures from there," Kolhe says. "In leukemia, stem cells get limboed in the blast state so you don't get any maturation. That means there are low platelets so you get clotting problems, you have low neutrophils so you have infections, you have less red blood cells so you get anemic," he says.
In fact, bleeding is a major cause of death for patients and often, significant gum bleeding is the first indicator.
The MCG researcher found one thing the blasts are producing is IDO.