Inhibiting a malfunctioning immune system pathway can kill diseased cells from patients with myelodysplastic syndrome (MDS), according to study results published July 8, 2013, in Cancer Cell.

In people with MDS, blood stem cells fail to mature into healthy red or white blood cells, which can lead to infections, anemia, bleeding disorders or acute myeloid leukemia (AML).  MDS can affect children but is more common in people over age 60.

The latest findings, based on laboratory tests involving mouse models and human MDS cells, suggest a new molecular target for drug designs. Currently the only cure for MDS is bone marrow transplant.

“Not only does our research implicate errant immune system signaling in MDS cells, it strongly indicates that inhibiting the function of this hijacked immune pathway may become an effective treatment option for MDS,” says Daniel Starczynowski, PhD, lead researcher and a member of the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s.

The research team verified that the immune system enzyme IRAK1 (Interleukin Receptor Associated Kinase-1) is highly over-expressed and hyper-activated in about 25 percent of MDS/AML cells. Further testing revealed that IRAK-Inh -- a small-molecule inhibitor of IRAK1 originally developed as a potential  treatment for chronic inflammation -- was effective at slowing disease progression.

However, the treatment did not overcome the effects of a pro-cancer survival gene called BCL2. In response, researchers tested IRAK-Inh in combination with an inhibitor of BCL2 called ABT-263. The combination treatment effectively killed MDS cells without harming normal blood cells.

Starczynowski cautioned that laboratory successes do not necessarily translate into safe and effective clinical treatments. Even if found to be effective, the potential treatment may not benefit all people with MDS because IRAK1 is thought to be overexpressed only in a subset of MDS patients.