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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. 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.
A review of 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, 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.
Stem cells in the bone marrow are supposed to mature into a variety of cells that enable human blood and immune system function. Instead in AML, stem cells get stuck in an in-between, undifferentiated state called blasts.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.
Bleeding is a major cause of death for patients and often, significant gum bleeding is the first indicator. The patients who died at six months had a high expression of IDO while the blasts produced relatively little IDO in the patients who lived five years or more. During pregnancy, cells in the placenta trigger an isolated suppression of the mother’s immune system so it won’t reject the genetically foreign fetus. They showed that IDO locally disables the mother’s immune system by degrading tryptophan, an amino acid essential to survival of T cells , orchestrators of the immune system’s response.
Later work would show that tumors – and leukemia – also use IDO to hide from the immune response. Conversely, some organ transplant patients who inexplicably express higher levels of IDO, have lower rejection rates of their new organ. Induction therapy is given to get the patient into remission, and is typically followed by more chemotherapy to ensure it stays dormant.
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