Elevated levels of natural immune suppressor is linked to poor survival of the leukemia patients


The researchers found that the patients diagnosed with high levels of immune suppressor enzyme have a short life-span. According to the findings published in the Nature Journal Scientific Reports, an indoleamine 2, 3 dioxygenase (IDO) inhibitor along with the standard therapy could be beneficial.

Dr. Ravindra Kolhe said, “We want to help people who are not responding to treatment and are dying very soon after their diagnosis.” He is the director of the Georgia Esoteric & Molecular Labs LLC in the Department of Pathology at the Medical College of Georgia.

On investigating about 40 patients with acute myeloid leukemia (AML), the researchers found that there was an increased risk of early mortality associated with the elevated levels of IDO enzyme. There was an increased IDO expression in the bone marrow biopsy observed in these patients. Thus the IDO expression should be routinely measured.

The researchers begin to explore the IDO inhibitor's clinical potential in these patients through clinical studies. Kolhe reported that they wanted to study about what is making leukemia aggressive that initial induction chemotherapy is not working.

"Early relapse tends to predict early mortality in these patients, and one of the things we looked at was IDO.” The cancer cells activate the disabler of the immune response (IDO gene) which is also used by the fetus and solid tumors.

In AML, the stem cells get stuck in an in-between, undifferentiated state called blast.  Kolhe said that these stem cells get limboed in the blast state, stop maturation and thus leads to lowered platelet count, neutrophils, and red blood cells.

IDO is an independent indicator if the other known variables are adjusted.” 

The blasts are produced by the IDO. On investigation, Kolhe found that the patients did not respond to chemotherapy due to the elevated IDO levels. The patients who died at six months had a high expression of IDO while the blasts produced little IDO in the patients who lived five years or more.

High IDO directly affects resistance to chemotherapy and in turn, affects the survival of the patients. The cells in the placenta trigger an isolated suppression of the mother's immune system. They also showed that IDO locally disables the mother's immune system by degrading tryptophan, reported in the journal Science.

In further studies, it would be shown that the IDO would play a role in hiding from the immune response. On the other hand, it was found that there were fewer chances of organ rejection in certain organ transplant patients if the IDO levels were higher.

According to the American Cancer Society, most patients (men) with AML are diagnosed at age 45. Induction therapy followed by chemotherapy could be beneficial to the patients, while certain patients might be cured with a stem cell transplant.