Lab Pinpoints New Drug Target for Infant Leukemia

Although many childhood leukemias are curable, one type – known as 11q23 infant leukemia – has a poor survival rate and requires intensive treatment with life-threatening side effects. In an early-edition article in Blood, the URMC shows it discovered a gene that could provide a new target for therapy.

Archibald S. Perkins, M.D., Ph.D., and Yi “Stanley” Zhang, Ph.D., in the Department of Pathology and Laboratory Medicine, reported that the MDS1-EVI1 (or PRDM3) protein is activated by the chromosomal mistakes that occur at 11q23, and is essential for the development of this leukemia. In mice they’ve explored the trail of molecular errors leading to MDS1-EVI1, and determined that an inhibitor of this gene would likely kill 11q23 infant leukemia in a targeted manner with little toxicity.

Perkins and Zhang are funded by New York State Stem Cell Science (NYSTEM). Recently the Children’s Leukemia Research Association of Long Island and Alex’s Lemonade Stand Foundation for Childhood Cancer based in Wynnewood, Pa., provided additional bridge funds so that Perkins’ lab could conduct the experiments needed to support a larger grant application to develop a targeted drug.

Findings in the Blood paper strongly suggest that other small-molecule inhibitors already in the pipeline could be tested as a treatment for 11q23 leukemia. They’re pursuing a high-throughput drug screen that would not only identify such novel drug candidates but weed out drugs with poor cell permeability or unknown toxicities, for example. Perkins hopes that collaborations with Stanford University and Memorial Sloan-Kettering will speed the process of improving treatment for a cancer that strikes about 2,000 infants a year in the U.S.